Mechanisms of Cancer-killing by Quercetin; A Review on Cell Death Mechanisms


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Cancer drug resistance has always been a serious issue regarding cancer research and therapy. Different cancers undergo different mutations, which may cause suppression of tumor suppressor genes, inhibition of apoptosis, stimulation of drug resistance mediators, and exhaustion of the immune system. The modulation of pro-death and survival-related mediators is an intriguing strategy for cancer therapy. Several nature-derived molecules, e.g., quercetin, have shown interesting properties against cancer through the modulation of apoptosis and autophagy mediators. Such molecules, e.g., quercetin, have been shown to stimulate apoptosis and other types of cell death pathways in cancers via the modulation of ROS metabolism. Quercetin may affect immune system function and trigger the expression and activity of tumor suppressor genes. Furthermore, it may suppress certain multidrug resistance mechanisms in cancer cells. This paper aims to review the effects of quercetin on various cell death mechanisms such as apoptosis, autophagic cell death, senescence, ferroptosis, and others.

Sobre autores

Hehua Wang

, Xinyang Vocational and Technical College

Autor responsável pela correspondência
Email: info@benthamscience.net

Ziyu Dong

, Xinyang Vocational and Technical College

Email: info@benthamscience.net

Jinhai Liu

, Xinyang Vocational and Technical College

Email: info@benthamscience.net

Zhaoyu Zhu

, Xinyang Vocational and Technical College

Autor responsável pela correspondência
Email: info@benthamscience.net

Masoud Najafi

Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108. doi: 10.3322/caac.21262 PMID: 25651787
  2. Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer, 2019, 144(8), 1941-1953. doi: 10.1002/ijc.31937 PMID: 30350310
  3. Rahib, L.; Wehner, M.R.; Matrisian, L.M.; Nead, K.T. Estimated projection of US cancer incidence and death to 2040. JAMA Netw. Open, 2021, 4(4), e214708-e214708. doi: 10.1001/jamanetworkopen.2021.4708 PMID: 33825840
  4. Castanon, A.; Landy, R.; Pesola, F.; Windridge, P.; Sasieni, P. Prediction of cervical cancer incidence in England, UK, up to 2040, under four scenarios: A modelling study. Lancet Public Health, 2018, 3(1), e34-e43. doi: 10.1016/S2468-2667(17)30222-0 PMID: 29307386
  5. Moding, E.J.; Kastan, M.B.; Kirsch, D.G. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat. Rev. Drug Discov., 2013, 12(7), 526-542. doi: 10.1038/nrd4003 PMID: 23812271
  6. Sadeghinezhad, S.; Khodamoradi, E.; Diojan, L.; Taeb, S.; Najafi, M. Radioprotective mechanisms of arbutin: A systematic review. Curr. Drug Res. Rev., 2022, 14(2), 132-138. doi: 10.2174/2589977514666220321114415 PMID: 35319405
  7. Lin, S.R.; Chang, C.H.; Hsu, C.F.; Tsai, M.J.; Cheng, H.; Leong, M.K.; Sung, P.J.; Chen, J.C.; Weng, C.F. Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. Br. J. Pharmacol., 2020, 177(6), 1409-1423. doi: 10.1111/bph.14816 PMID: 31368509
  8. Bracci, L.; Fabbri, A.; Del Cornò, M.; Conti, L. Dietary polyphenols: Promising adjuvants for colorectal cancer therapies. Cancers, 2021, 13(18), 4499. doi: 10.3390/cancers13184499 PMID: 34572726
  9. Moslehi, M.; Moazamiyanfar, R.; Dakkali, M.S.; Rezaei, S.; Rastegar-Pouyani, N.; Jafarzadeh, E.; Mouludi, K.; Khodamoradi, E.; Taeb, S.; Najafi, M. Modulation of the immune system by melatonin; implications for cancer therapy. Int. Immunopharmacol., 2022, 108, 108890. doi: 10.1016/j.intimp.2022.108890 PMID: 35623297
  10. Taeb, S.; Ashrafizadeh, M.; Zarrabi, A.; Rezapoor, S.; Musa, A.E.; Farhood, B.; Najafi, M. Role of tumor microenvironment in cancer stem cells resistance to radiotherapy. Curr. Cancer Drug Targets, 2022, 22(1), 18-30. doi: 10.2174/1568009622666211224154952 PMID: 34951575
  11. Turchan, W.T.; Pitroda, S.P.; Weichselbaum, R.R. Treatment of cancer with radio-immunotherapy: What we currently know and what the future may hold. Int. J. Mol. Sci., 2021, 22(17), 9573. doi: 10.3390/ijms22179573 PMID: 34502479
  12. Amini, P.; Moazamiyanfar, R.; Dakkali, M.S.; Khani, A.; Jafarzadeh, E.; Mouludi, K.; Khodamoradi, E.; Johari, R.; Taeb, S.; Najafi, M. Resveratrol in cancer therapy; from stimulation of genomic stability to adjuvant cancer therapy; a comprehensive review. Curr. Top. Med. Chem., 2022. PMID: 36239730
  13. Moslehi, M.; Rezaei, S.; Talebzadeh, P.; Ansari, M.J.; Jawad, M.A.; Jalil, A.T.; Rastegar-Pouyani, N.; Jafarzadeh, E.; Taeb, S.; Najafi, M. Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms. Clin. Exp. Pharmacol. Physiol., 2022, 1440-1681.13725. doi: 10.1111/1440-1681.13725 PMID: 36111951
  14. Rose, B.S.; Aydogan, B.; Liang, Y.; Yeginer, M.; Hasselle, M.D.; Dandekar, V.; Bafana, R.; Yashar, C.M.; Mundt, A.J.; Roeske, J.C. Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Int. J. Radiat. Oncol. Biol. Phys., 2011, 79(3), 800-807.
  15. Lai, X.; Najafi, M. Redox interactions in chemo/radiation therapy-induced lung toxicity; mechanisms and therapy perspectives. Curr. Drug Targets, 2022, 23(13), 1261-1276. doi: 10.2174/1389450123666220705123315 PMID: 35792117
  16. Xu, C.; Najafi, M.; Shang, Z. Lung pneumonitis and fibrosis in cancer therapy; a review on cellular and molecular mechanisms. Curr. Drug Targets, 2022, 23(16), 1505-1525. doi: 10.2174/1389450123666220907144131 PMID: 36082868
  17. Mortezaee, K.; Shabeeb, D.; Musa, A.E.; Najafi, M.; Farhood, B. Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr. Clin. Pharmacol., 2019, 14(1), 41-53. doi: 10.2174/1574884713666181025141559 PMID: 30360725
  18. Huang, J.; Chen, X.; Chang, Z.; Xiao, C.; Najafi, M. Boosting anti-tumour immunity using adjuvant apigenin. Anticancer. Agents Med. Chem., 2022, 22. doi: 10.2174/1871520622666220523151409 PMID: 35616683
  19. Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Shabeeb, D.; Musa, A.E. Resveratrol as an adjuvant for normal tissues protection and tumor sensitization. Curr. Cancer Drug Targets, 2020, 20(2), 130-145. doi: 10.2174/1568009619666191019143539 PMID: 31738153
  20. Abotaleb, M.; Samuel, S.; Varghese, E.; Varghese, S.; Kubatka, P.; Liskova, A.; Büsselberg, D. Flavonoids in cancer and apoptosis. Cancers, 2018, 11(1), 28. doi: 10.3390/cancers11010028 PMID: 30597838
  21. Park, E.-J.; Pezzuto, MJ. Flavonoids in cancer prevention. Anticancer. Agents. Med. Chem., 2012, 12(8), 836-851.
  22. Baghel, S.S.; Shrivastava, N.; Baghel, R.S.; Agrawal, P.; Rajput, S. A review of quercetin: Antioxidant and anticancer properties. World J. Pharm. Pharm. Sci., 2012, 1(1), 146-160.
  23. Brito, A.; Ribeiro, M.; Abrantes, A.; Pires, A.; Teixo, R.; Tralhão, J.; Botelho, M. Quercetin in cancer treatment, alone or in combination with conventional therapeutics? Curr. Med. Chem., 2015, 22(26), 3025-3039. doi: 10.2174/0929867322666150812145435 PMID: 26264923
  24. Erlund, I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr. Res., 2004, 24(10), 851-874. doi: 10.1016/j.nutres.2004.07.005
  25. Nishimuro, H.; Ohnishi, H.; Sato, M.; Ohnishi-Kameyama, M.; Matsunaga, I.; Naito, S.; Ippoushi, K.; Oike, H.; Nagata, T.; Akasaka, H.; Saitoh, S.; Shimamoto, K.; Kobori, M. Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients, 2015, 7(4), 2345-2358. doi: 10.3390/nu7042345 PMID: 25849945
  26. Ganeshpurkar, A.; Saluja, A.K. The pharmacological potential of rutin. Saudi. Pharm. J., 2017, 25(2), 149-164.
  27. Parasuraman, S.; Anand David, A.V.; Arulmoli, R. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn. Rev., 2016, 10(20), 84-89. doi: 10.4103/0973-7847.194044 PMID: 28082789
  28. Kaşıkcı, M.B.; Bağdatlıoğlu, N. Bioavailability of quercetin. Current research in nutrition and food science journal,2016, 4. Special Issue Nutrition in Conference, 2016, (October), 146-151.
  29. Kashyap, D.; Garg, V.K.; Tuli, H.S.; Yerer, M.B.; Sak, K.; Sharma, A.K.; Kumar, M.; Aggarwal, V.; Sandhu, S.S. Fisetin and quercetin: promising flavonoids with chemopreventive potential. Biomolecules, 2019, 9(5), 174. doi: 10.3390/biom9050174 PMID: 31064104
  30. Xiao, L.; Luo, G.; Tang, Y.; Yao, P. Quercetin and iron metabolism: What we know and what we need to know. Food Chem. Toxicol., 2018, 114, 190-203. doi: 10.1016/j.fct.2018.02.022 PMID: 29432835
  31. Sanders, R.A.; Rauscher, F.M.; Watkins, J.B., III. Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats. J. Biochem. Mol. Toxicol., 2001, 15(3), 143-149. doi: 10.1002/jbt.11 PMID: 11424224
  32. Xu, D.; Hu, M.J.; Wang, Y.Q.; Cui, Y.L. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules, 2019, 24(6), 1123. doi: 10.3390/molecules24061123 PMID: 30901869
  33. Dower, J.I.; Geleijnse, J.M.; Gijsbers, L.; Schalkwijk, C.; Kromhout, D.; Hollman, P.C. Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre) hypertensive adults: a randomized double-blind, placebo-controlled, crossover trial. J. Nutr., 2015, 145(7), 1459-1463. doi: 10.3945/jn.115.211888 PMID: 25972527
  34. Gibellini, L.; Pinti, M.; Nasi, M.; Montagna, J.P.; De Biasi, S.; Roat, E.; Bertoncelli, L.; Cooper, E.L.; Cossarizza, A. Quercetin and cancer chemoprevention. Evid. Based Complement. Alternat. Med., 2011, 2011, 1-15. doi: 10.1093/ecam/neq053 PMID: 21792362
  35. Wu, L.; Zhang, Q.; Mo, W.; Feng, J.; Li, S.; Li, J.; Liu, T.; Xu, S.; Wang, W.; Lu, X.; Yu, Q.; Chen, K.; Xia, Y.; Lu, J.; Xu, L.; Zhou, Y.; Fan, X.; Guo, C. Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-β1/Smads and PI3K/Akt pathways. Sci. Rep., 2017, 7(1), 9289. doi: 10.1038/s41598-017-09673-5 PMID: 28839277
  36. Bhadoriya, S.S.; Mangal, A.; Madoriya, N.; Dixit, P. Bioavailability and bioactivity enhancement of herbal drugs by "Nanotechnology": A review. J Curr Pharm Res, 2011, 8, 1-7.
  37. Chen, L.; Cao, H.; Huang, Q.; Xiao, J.; Teng, H. Absorption, metabolism and bioavailability of flavonoids: A review. Crit. Rev. Food Sci. Nutr., 2022, 62(28), 7730-7742. PMID: 34078189
  38. Ren, K.W.; Li, Y.H.; Wu, G.; Ren, J.Z.; Lu, H.B.; Li, Z.M.; Han, X.W. Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells. Int. J. Oncol., 2017, 50(4), 1299-1311. doi: 10.3892/ijo.2017.3886 PMID: 28259895
  39. Nan, W.; Ding, L.; Chen, H.; Khan, F.U.; Yu, L.; Sui, X.; Shi, X. Topical use of quercetin-loaded chitosan nanoparticles against ultraviolet b radiation. Front. Pharmacol., 2018, 9, 826. doi: 10.3389/fphar.2018.00826 PMID: 30140227
  40. Amanzadeh, E.; Esmaeili, A.; Abadi, R.E.N.; Kazemipour, N.; Pahlevanneshan, Z.; Beheshti, S. Quercetin conjugated with superparamagnetic iron oxide nanoparticles improves learning and memory better than free quercetin via interacting with proteins involved in LTP. Sci. Rep., 2019, 9(1), 6876. doi: 10.1038/s41598-019-43345-w PMID: 31053743
  41. Guan, X.; Gao, M.; Xu, H.; Zhang, C.; Liu, H.; Lv, L.; Deng, S.; Gao, D.; Tian, Y. Quercetin-loaded poly (lactic-co-glycolic acid)- D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for the targeted treatment of liver cancer. Drug Deliv., 2016, 23(9), 3307-3318. doi: 10.1080/10717544.2016.1176087 PMID: 27067032
  42. Zhao, S.; Tang, Y.; Wang, R.; Najafi, M. Mechanisms of cancer cell death induction by paclitaxel: An updated review. Apoptosis, 2022, 27(9-10), 647-667. doi: 10.1007/s10495-022-01750-z PMID: 35849264
  43. Tan, B.J.; Liu, Y.; Chang, K.L.; Lim, B.K.; Chiu, G.N. Perorally active nanomicellar formulation of quercetin in the treatment of lung cancer. Int. J. Nanomedicine, 2012, 7, 651-661. PMID: 22334787
  44. Jangde, R.; Singh, D. Preparation and optimization of quercetin-loaded liposomes for wound healing, using response surface methodology. Artif. Cells Nanomed. Biotechnol., 2016, 44(2), 635-641. doi: 10.3109/21691401.2014.975238 PMID: 25375215
  45. Weiss-Angeli, V.; Poletto, F.S.; Marco, S.L.; Salvador, M.; Silveira, N.P.; Guterres, S.S.; Pohlmann, A.R. Sustained antioxidant activity of quercetin-loaded lipid-core nanocapsules. J. Nanosci. Nanotechnol., 2012, 12(3), 2874-2880. doi: 10.1166/jnn.2012.5770 PMID: 22755137
  46. Dian, L.; Yu, E.; Chen, X.; Wen, X.; Zhang, Z.; Qin, L.; Wang, Q.; Li, G.; Wu, C. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles. Nanoscale Res. Lett., 2014, 9(1), 684. doi: 10.1186/1556-276X-9-684 PMID: 26088982
  47. Schwendener, R.A.; Schott, H. Liposome formulations of hydrophobic drugs. Methods Mol. Biol., 2010, 605, 129-138. doi: 10.1007/978-1-60327-360-2_8 PMID: 20072877
  48. Eloy, J.O.; Claro de Souza, M.; Petrilli, R.; Barcellos, J.P.A.; Lee, R.J.; Marchetti, J.M. Liposomes as carriers of hydrophilic small molecule drugs: Strategies to enhance encapsulation and delivery. Colloids Surf. B Biointerfaces, 2014, 123, 345-363. doi: 10.1016/j.colsurfb.2014.09.029 PMID: 25280609
  49. Men, K.; Duan, X.; Wei, Wei. Nanoparticle-delivered quercetin for cancer therapy. Anticancer. Agents. Med. Chem., 2014, 14(6), 826-832.
  50. Jan, A.T.; Kamli, M.R.; Murtaza, I.; Singh, J.B.; Ali, A.; Haq, Q.M.R. Dietary flavonoid quercetin and associated health benefits-An overview. Food Rev. Int., 2010, 26(3), 302-317. doi: 10.1080/87559129.2010.484285
  51. Miles, S.L.; McFarland, M.; Niles, R.M. Molecular and physiological actions of quercetin: need for clinical trials to assess its benefits in human disease. Nutr. Rev., 2014, 72(11), 720-734. doi: 10.1111/nure.12152 PMID: 25323953
  52. Zhou, Y.; Suo, W.; Zhang, X.; Lv, J.; Liu, Z.; Liu, R. Roles and mechanisms of quercetin on cardiac arrhythmia: A review. Biomed. Pharmacother., 2022, 153, 113447. doi: 10.1016/j.biopha.2022.113447 PMID: 36076562
  53. Panpan, T.; Yuchen, D.; Xianyong, S.; Meng, L.; Ruijuan, H.; Ranran, D.; Pengyan, Z.; Mingxi, L.; Rongrong, X. Cardiac remodelling following cancer therapy: A review. Cardiovasc. Toxicol., 2022, 22(9), 771-786. doi: 10.1007/s12012-022-09762-6 PMID: 35877038
  54. Ashrafizadeh, M.; Samarghandian, S.; Hushmandi, K.; Zabolian, A.; Shahinozzaman, M.; Saleki, H.; Esmaeili, H.; Raei, M.; Entezari, M.; Zarrabi, A.; Najafi, M. Quercetin in attenuation of ischemic/reperfusion injury: A review. Curr. Mol. Pharmacol., 2021, 14(4), 537-558. doi: 10.2174/1874467213666201217122544 PMID: 33334302
  55. Verma, S.; Dutta, A.; Dahiya, A.; Kalra, N. Quercetin-3-Rutinoside alleviates radiation-induced lung inflammation and fibrosis via regulation of NF-κB/TGF-β1 signaling. Phytomedicine, 2022, 99, 154004. doi: 10.1016/j.phymed.2022.154004 PMID: 35219007
  56. Qin, M.; Chen, W.; Cui, J.; Li, W.; Liu, D.; Zhang, W. Protective efficacy of inhaled quercetin for radiation pneumonitis. Exp. Ther. Med., 2017, 14(6), 5773-5778. doi: 10.3892/etm.2017.5290 PMID: 29285120
  57. Lotfi, M.; Kazemi, S.; Ebrahimpour, A.; Shirafkan, F.; Pirzadeh, M.; Hosseini, M.; Moghadamnia, A.A. Protective effect of quercetin nanoemulsion on 5-fluorouracil-induced oral mucositis in mice. J. Oncol., 2021. Available from: https://www.hindawi.com/journals/jo/2021/5598230/
  58. Baran, M.; Yay, A.; Onder, G.O.; canturk Tan, F.; Yalcin, B.; Balcioglu, E.; Yıldız, O.G. Hepatotoxicity and renal toxicity induced by radiation and the protective effect of quercetin in male albino rats. Int. J. Radiat. Biol., 2022, 98(9), 1473-1483.
  59. Najafi, M.; Tavakol, S.; Zarrabi, A.; Ashrafizadeh, M. Dual role of quercetin in enhancing the efficacy of cisplatin in chemotherapy and protection against its side effects: A review. Arch. Physiol. Biochem., 2022, 128(6), 1438-1452. doi: 10.1080/13813455.2020.1773864 PMID: 32521182
  60. Zhivotovsky, B.; Orrenius, S. Cell death mechanisms: Cross-talk and role in disease. Exp. Cell Res., 2010, 316(8), 1374-1383. doi: 10.1016/j.yexcr.2010.02.037 PMID: 20211164
  61. Shah, B.P.; Pasquale, N.; De, G.; Tan, T.; Ma, J.; Lee, K.B. Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis. ACS Nano, 2014, 8(9), 9379-9387. doi: 10.1021/nn503431x PMID: 25133971
  62. Huang, J.; Chang, Z.; Lu, Q.; Chen, X.; Najafi, M. Nobiletin as an inducer of programmed cell death in cancer: A review. Apoptosis, 2022, 27(5-6), 297-310. doi: 10.1007/s10495-022-01721-4 PMID: 35312885
  63. Sinha, D.; Duijf, P.H.G.; Khanna, K.K. Mitotic slippage: An old tale with a new twist. Cell Cycle, 2019, 18(1), 7-15. doi: 10.1080/15384101.2018.1559557 PMID: 30601084
  64. Ashrafizadeh, M.; Farhood, B.; Eleojo Musa, A.; Taeb, S.; Rezaeyan, A.; Najafi, M. Abscopal effect in radioimmunotherapy. Int. Immunopharmacol., 2020, 85, 106663. doi: 10.1016/j.intimp.2020.106663 PMID: 32521494
  65. Ashrafizadeh, M.; Farhood, B.; Eleojo Musa, A.; Taeb, S.; Najafi, M. Damage-associated molecular patterns in tumor radiotherapy. Int. Immunopharmacol., 2020, 86, 106761. doi: 10.1016/j.intimp.2020.106761 PMID: 32629409
  66. Mortezaee, K.; Parwaie, W.; Motevaseli, E.; Mirtavoos-Mahyari, H.; Musa, A.E.; Shabeeb, D.; Esmaely, F.; Najafi, M.; Farhood, B. Targets for improving tumor response to radiotherapy. Int. Immunopharmacol., 2019, 76, 105847. doi: 10.1016/j.intimp.2019.105847 PMID: 31466051
  67. De Palma, M.; Biziato, D.; Petrova, T.V. Microenvironmental regulation of tumour angiogenesis. Nat. Rev. Cancer, 2017, 17(8), 457-474. doi: 10.1038/nrc.2017.51 PMID: 28706266
  68. Nishikawa, M. Reactive oxygen species in tumor metastasis. Cancer Lett., 2008, 266(1), 53-59. doi: 10.1016/j.canlet.2008.02.031 PMID: 18362051
  69. Moloney, J.N.; Cotter, T.G. Semin Cell Dev Biol; Elsevier: Amsterdam, 2018, Vol. 80, pp. 50-64.
  70. Kopustinskiene, D.M.; Jakstas, V.; Savickas, A.; Bernatoniene, J. Flavonoids as anticancer agents. Nutrients, 2020, 12(2), 457. doi: 10.3390/nu12020457 PMID: 32059369
  71. Wu, Q.; Needs, P.W.; Lu, Y.; Kroon, P.A.; Ren, D.; Yang, X. Different antitumor effects of quercetin, quercetin-3′-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Funct., 2018, 9(3), 1736-1746. doi: 10.1039/C7FO01964E PMID: 29497723
  72. Zhang, H.; Zhang, M.; Yu, L.; Zhao, Y.; He, N.; Yang, X. Antitumor activities of quercetin and quercetin-5′,8-disulfonate in human colon and breast cancer cell lines. Food Chem. Toxicol., 2012, 50(5), 1589-1599. doi: 10.1016/j.fct.2012.01.025 PMID: 22310237
  73. Cheki, M.; Yahyapour, R.; Farhood, B.; Rezaeyan, A.; Shabeeb, D.; Amini, P.; Rezapoor, S.; Najafi, M. COX-2 in radiotherapy: A potential target for radioprotection and radiosensitization. Curr. Mol. Pharmacol., 2018, 11(3), 173-183. doi: 10.2174/1874467211666180219102520 PMID: 29468988
  74. Raja, S.B.; Rajendiran, V.; Kasinathan, N.K.; P, A.; Venkatabalasubramanian, S.; Murali, M.R.; Devaraj, H.; Devaraj, S.N. Differential cytotoxic activity of quercetin on colonic cancer cells depends on ROS generation through COX-2 expression. Food Chem. Toxicol., 2017, 106(Pt A), 92-106. doi: 10.1016/j.fct.2017.05.006 PMID: 28479391
  75. Fu, X.; Li, M.; Tang, C.; Huang, Z.; Najafi, M. Targeting of cancer cell death mechanisms by resveratrol: A review. Apoptosis, 2021, 26(11-12), 561-573. doi: 10.1007/s10495-021-01689-7 PMID: 34561763
  76. Zhang, X.; Huang, J.; Yu, C.; Xiang, L.; Li, L.; Shi, D.; Lin, F. Quercetin enhanced paclitaxel therapeutic effects towards PC-3 Prostate cancer through er stress induction and ROS production. OncoTargets Ther., 2020, 13, 513-523. doi: 10.2147/OTT.S228453 PMID: 32021294
  77. Bishayee, K.; Ghosh, S.; Mukherjee, A.; Sadhukhan, R.; Mondal, J.; Khuda-Bukhsh, A.R. Quercetin induces cytochrome‐c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: Signal cascade and drug‐DNA interaction. Cell Prolif., 2013, 46(2), 153-163. doi: 10.1111/cpr.12017 PMID: 23510470
  78. Srivastava, S.; Somasagara, R.R.; Hegde, M.; Nishana, M.; Tadi, S.K.; Srivastava, M.; Choudhary, B.; Raghavan, S.C. Quercetin, a natural flavonoid interacts with dna, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci. Rep., 2016, 6(1), 24049. doi: 10.1038/srep24049 PMID: 27068577
  79. Niazvand, F.; Orazizadeh, M.; Khorsandi, L.; Abbaspour, M.; Mansouri, E.; Khodadadi, A. Effects of quercetin-loaded nanoparticles on MCF-7 human breast cancer cells. Medicina, 2019, 55(4), 114. doi: 10.3390/medicina55040114 PMID: 31013662
  80. Jeon, J.S.; Kwon, S.; Ban, K.; Kwon Hong, Y.; Ahn, C.; Sung, J.S.; Choi, I. Regulation of the intracellular ROS level is critical for the antiproliferative effect of quercetin in the hepatocellular carcinoma cell line HepG2. Nutr. Cancer, 2019, 71(5), 861-869. doi: 10.1080/01635581.2018.1559929 PMID: 30661409
  81. Li, N.; Sun, C.; Zhou, B.; Xing, H.; Ma, D.; Chen, G.; Weng, D. Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer. PLoS One, 2014, 9(7), e100314. doi: 10.1371/journal.pone.0100314 PMID: 24999622
  82. Chang, Y.F.; Chi, C.W.; Wang, J.J. Reactive oxygen species production is involved in quercetin-induced apoptosis in human hepatoma cells. Nutr. Cancer, 2006, 55(2), 201-209. doi: 10.1207/s15327914nc5502_12 PMID: 17044776
  83. Macip, S.; Igarashi, M.; Berggren, P.; Yu, J.; Lee, S.W.; Aaronson, S.A. Influence of induced reactive oxygen species in p53-mediated cell fate decisions. Mol. Cell. Biol., 2003, 23(23), 8576-8585. doi: 10.1128/MCB.23.23.8576-8585.2003 PMID: 14612402
  84. Sun, J.; Feng, Y.; Wang, Y.; Ji, Q.; Cai, G.; Shi, L.; Wang, Y.; Huang, Y.; Zhang, J.; Li, Q. α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation. Int. J. Oncol., 2019, 54(5), 1601-1612. doi: 10.3892/ijo.2019.4757 PMID: 30896843
  85. Law, B.Y.K.; Gordillo-Martínez, F.; Qu, Y.Q.; Zhang, N.; Xu, S.W.; Coghi, P.S.; Fai Mok, S.W.; Guo, J.; Zhang, W.; Leung, E.L.H.; Fan, X.X.; Wu, A.G.; Chan, W.K.; Yao, X.J.; Wang, J.R.; Liu, L.; Wong, V.K.W. Thalidezine, a novel AMPK activator, eliminates apoptosis-resistant cancer cells through energy-mediated autophagic cell death. Oncotarget, 2017, 8(18), 30077-30091. doi: 10.18632/oncotarget.15616 PMID: 28404910
  86. Kim, G.T.; Lee, S.H.; Kim, Y.M. Quercetin regulates sestrin 2-ampk-mtor signaling pathway and induces apoptosis via increased intracellular ros in hct116 colon cancer cells. J. Cancer Prev., 2013, 18(3), 264-270. doi: 10.15430/JCP.2013.18.3.264 PMID: 25337554
  87. Kim, G.T.; Lee, S.H.; Kim, J.; Kim, Y.M. Quercetin regulates the sestrin 2-AMPK-p38 MAPK signaling pathway and induces apoptosis by increasing the generation of intracellular ROS in a p53-independent manner. Int. J. Mol. Med., 2014, 33(4), 863-869. doi: 10.3892/ijmm.2014.1658 PMID: 24535669
  88. Yi, L.; Zongyuan, Y.; Cheng, G.; Lingyun, Z.; GuiLian, Y.; Wei, G. Quercetin enhances apoptotic effect of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) in ovarian cancer cells through reactive oxygen species (ROS) mediated CCAAT enhancer‐binding protein homologous protein (CHOP)‐death receptor 5 pathway. Cancer Sci., 2014, 105(5), 520-527. doi: 10.1111/cas.12395 PMID: 24612139
  89. Wang, L.H.; Wu, C.F.; Rajasekaran, N.; Shin, Y.K. Loss of tumor suppressor gene function in human cancer: An overview. Cell. Physiol. Biochem., 2018, 51(6), 2647-2693. doi: 10.1159/000495956 PMID: 30562755
  90. Yogosawa, S.; Yoshida, K. Tumor suppressive role for kinases phosphorylating p53 in DNA damage‐induced apoptosis. Cancer Sci., 2018, 109(11), 3376-3382. doi: 10.1111/cas.13792 PMID: 30191640
  91. Philippe, G.J.B.; Mittermeier, A.; Lawrence, N.; Huang, Y.H.; Condon, N.D.; Loewer, A.; Craik, D.J.; Henriques, S.T. Angler peptides: macrocyclic conjugates inhibit p53: MDM2/X interactions and activate apoptosis in cancer cells. ACS Chem. Biol., 2021, 16(2), 414-428. doi: 10.1021/acschembio.0c00988 PMID: 33533253
  92. Cordani, M.; Butera, G.; Pacchiana, R.; Masetto, F.; Mullappilly, N.; Riganti, C.; Donadelli, M. Mutant p53-associated molecular mechanisms of ROS regulation in cancer cells. Biomolecules, 2020, 10(3), 361. doi: 10.3390/biom10030361 PMID: 32111081
  93. Papa, A.; Pandolfi, P.P. The PTEN-PI3K axis in cancer. Biomolecules, 2019, 9(4), 153. doi: 10.3390/biom9040153 PMID: 30999672
  94. Tanigawa, S.; Fujii, M.; Hou, D.X. Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in HepG2 cells. Biosci. Biotechnol. Biochem., 2008, 72(3), 797-804. doi: 10.1271/bbb.70680 PMID: 18323654
  95. Vidya Priyadarsini, R.; Senthil Murugan, R.; Maitreyi, S.; Ramalingam, K.; Karunagaran, D.; Nagini, S. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur. J. Pharmacol., 2010, 649(1-3), 84-91. doi: 10.1016/j.ejphar.2010.09.020 PMID: 20858478
  96. Kuo, P.C.; Liu, H.F.; Chao, J.I. Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J. Biol. Chem., 2004, 279(53), 55875-55885. doi: 10.1074/jbc.M407985200 PMID: 15456784
  97. Lim, J.H.; Park, J.W.; Min, D.S.; Chang, J.S.; Lee, Y.H.; Park, Y.B.; Choi, K.S.; Kwon, T.K. NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells. Apoptosis, 2007, 12(2), 411-421. doi: 10.1007/s10495-006-0576-9 PMID: 17191121
  98. Xavier, C.P.R.; Lima, C.F.; Rohde, M.; Pereira-Wilson, C. Quercetin enhances 5-fluorouracil-induced apoptosis in MSI colorectal cancer cells through p53 modulation. Cancer Chemother. Pharmacol., 2011, 68(6), 1449-1457. doi: 10.1007/s00280-011-1641-9 PMID: 21479885
  99. Wang, G.; Zhang, J.; Liu, L.; Sharma, S.; Dong, Q. Quercetin potentiates doxorubicin mediated antitumor effects against liver cancer through p53/Bcl-xl. PLoS One, 2012, 7(12), e51764. doi: 10.1371/journal.pone.0051764 PMID: 23240061
  100. Gong, C.; Yang, Z.; Zhang, L.; Wang, Y.; Gong, W.; Liu, Y. Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway. OncoTargets Ther., 2017, 11, 17-27. doi: 10.2147/OTT.S147316 PMID: 29317830
  101. Liu, B.; Chen, Y.; St Clair, D.K. ROS and p53: A versatile partnership. Free Radic. Biol. Med., 2008, 44(8), 1529-1535. doi: 10.1016/j.freeradbiomed.2008.01.011 PMID: 18275858
  102. Ward, A.B.; Mir, H.; Kapur, N.; Gales, D.N.; Carriere, P.P.; Singh, S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J. Surg. Oncol., 2018, 16(1), 108. doi: 10.1186/s12957-018-1400-z PMID: 29898731
  103. Bishayee, K.; Khuda-Bukhsh, A.R.; Huh, S.O. PLGA-Loaded gold-nanoparticles precipitated with quercetin downregulate HDAC-Akt activities controlling proliferation and activate p53-ROS crosstalk to induce apoptosis in hepatocarcinoma cells. Mol. Cells, 2015, 38(6), 518-527. doi: 10.14348/molcells.2015.2339 PMID: 25947292
  104. Gulati, N.; Laudet, B.; Zohrabian, V.M.; Murali, R.; Jhanwar-Uniyal, M. The antiproliferative effect of Quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway. Anticancer Res., 2006, 26(2A), 1177-1181. PMID: 16619521
  105. Miao, Z.; Miao, Z.; Wang, S.; Shi, X.; Xu, S. Quercetin antagonizes imidacloprid-induced mitochondrial apoptosis through PTEN/PI3K/AKT in grass carp hepatocytes. Environ. Pollut., 2021, 290, 118036. doi: 10.1016/j.envpol.2021.118036 PMID: 34488159
  106. Li, S.-z.; Qiao, S.-f.; Zhang, J.-h.; Li, K. Quercetin increase the chemosensitivity of breast cancer cells to doxorubicin via PTEN/Akt pathway. Anticancer. Agents. Med. Chem., 2015, 15(9), 1185-1189.
  107. Ashrafizadeh, M.; Farhood, B.; Eleojo Musa, A.; Taeb, S.; Najafi, M. The interactions and communications in tumor resistance to radiotherapy: Therapy perspectives. Int. Immunopharmacol., 2020, 87, 106807. doi: 10.1016/j.intimp.2020.106807 PMID: 32683299
  108. Aung, M.O.M.H.; Mat Nor, N.; Mohd Adnan, L.H.; Ahmad, N.Z.B.; Septama, A.W.; Nik Nurul Najihah, N.N.N.; Ohn, M.L.; Simbak, N. Effects of apigenin, luteolin, and quercetin on the natural killer (NK-92) cells proliferation: A potential role as immunomodulator. Sains Malays., 2021, 50(3), 821-828. doi: 10.17576/jsm-2021-5003-22
  109. Yu, C.S.; Yang, J.S.; Kuo, H.M.; Chung, J.G. Quercetin promoted natural killer cells activity and inhibits WEHI‐3 leukemia cells in Balb/C mice in vivo. FASEB J., 2007, 21(6), A1189-A1189. doi: 10.1096/fasebj.21.6.A1189-a
  110. Bae, J.H.; Kim, J.Y.; Kim, M.J.; Chang, S.H.; Park, Y.S.; Son, C.H.; Park, S.J.; Chung, J.S.; Lee, E.Y.; Kim, S.H.; Kang, C.D. Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J. Immunother., 2010, 33(4), 391-401. doi: 10.1097/CJI.0b013e3181d32f22 PMID: 20386467
  111. Kim, Y.H.; Lee, Y.J. TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation. J. Cell. Biochem., 2007, 100(4), 998-1009. doi: 10.1002/jcb.21098 PMID: 17031854
  112. Askar, M.A.; El-Nashar, H.A.S.; Al-Azzawi, M.A.; Rahman, S.S.A.; Elshawi, O.E. Synergistic effect of quercetin magnetite nanoparticles and targeted radiotherapy in treatment of breast cancer. Breast Cancer, 2022, 16, 11782234221086728. doi: 10.1177/11782234221086728 PMID: 35359610
  113. Mortezaee, K.; Najafi, M. Immune system in cancer radiotherapy: Resistance mechanisms and therapy perspectives. Crit. Rev. Oncol. Hematol., 2021, 157, 103180. doi: 10.1016/j.critrevonc.2020.103180 PMID: 33264717
  114. Riganti, C.; Contino, M. New strategies to overcome resistance to chemotherapy and immune system in cancer. Int. J. Mol. Sci., 2019, 20(19), 4783.
  115. Jing, L.; Lin, J.; Yang, Y.; Tao, L.; Li, Y.; Liu, Z.; Zhao, Q.; Diao, A. Quercetin inhibiting the PD‐1/PD‐L1 interaction for immune‐enhancing cancer chemopreventive agent. Phytother. Res., 2021, 35(11), 6441-6451. doi: 10.1002/ptr.7297 PMID: 34560814
  116. Tan, C.; Hu, W.; He, Y.; Zhang, Y.; Zhang, G.; Xu, Y.; Tang, J. Cytokine-mediated therapeutic resistance in breast cancer. Cytokine, 2018, 108, 151-159. doi: 10.1016/j.cyto.2018.03.020 PMID: 29609137
  117. Liang, S.; Chen, Z.; Jiang, G.; Zhou, Y.; Liu, Q.; Su, Q.; Wei, W.; Du, J.; Wang, H. Activation of GPER suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-κB/IL-6 signals. Cancer Lett., 2017, 386, 12-23. doi: 10.1016/j.canlet.2016.11.003 PMID: 27836733
  118. Jones, V.S.; Huang, R-Y.; Chen, L-P.; Chen, Z-S.; Fu, L.; Huang, R-P. Cytokines in cancer drug resistance: Cues to new therapeutic strategies. Biochim. Biophys. Acta, 2016, 1865(2), 255-265. PMID: 26993403
  119. Balakrishnan, S.; Mukherjee, S.; Das, S.; Bhat, F.A.; Raja Singh, P.; Patra, C.R.; Arunakaran, J. Gold nanoparticles-conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt-mediated pathway in breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochem. Funct., 2017, 35(4), 217-231. doi: 10.1002/cbf.3266 PMID: 28498520
  120. Shi, H.; Li, X.Y.; Chen, Y.; Zhang, X.; Wu, Y.; Wang, Z.X.; Chen, P.H.; Dai, H.Q.; Feng, J.; Chatterjee, S.; Li, Z.J.; Huang, X.W.; Wei, H.Q.; Wang, J.; Lu, G.D.; Zhou, J. Quercetin induces apoptosis via downregulation of vascular endothelial growth Factor/Akt signaling pathway in acute myeloid leukemia cells. Front. Pharmacol., 2020, 11, 534171. doi: 10.3389/fphar.2020.534171 PMID: 33362534
  121. Cao, L.; Yang, Y.; Ye, Z.; Lin, B.; Zeng, J.; Li, C.; Liang, T.; Zhou, K.; Li, J. Quercetin-3-methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways. Int. J. Mol. Med., 2018, 42(3), 1625-1636. doi: 10.3892/ijmm.2018.3741 PMID: 29956731
  122. Senthilkumar, K.; Elumalai, P.; Arunkumar, R.; Banudevi, S.; Gunadharini, N.D.; Sharmila, G.; Selvakumar, K.; Arunakaran, J. Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol. Cell. Biochem., 2010, 344(1-2), 173-184. doi: 10.1007/s11010-010-0540-4 PMID: 20658310
  123. Lu, X.; Yang, F.; Chen, D.; Zhao, Q.; Chen, D.; Ping, H.; Xing, N. Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. Int. J. Biol. Sci., 2020, 16(7), 1121-1134. doi: 10.7150/ijbs.41686 PMID: 32174789
  124. Safi, A.; Heidarian, E.; Ahmadi, R. Quercetin synergistically enhances the anticancer efficacy of docetaxel through induction of apoptosis and modulation of PI3K/AKT, MAPK/ERK, and JAK/STAT3 signaling pathways in MDA-MB-231 breast cancer cell line. Int. J. Mol. Cell. Med., 2021, 10(1), 11-22. PMID: 34268250
  125. Lan, C-Y.; Chen, S-Y.; Kuo, C-W.; Lu, C-C.; Yen, G-C. Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells. Yao Wu Shi Pin Fen Xi, 2019, 27(4), 887-896. PMID: 31590760
  126. Fan, Y.; Mao, R.; Yang, J. NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell, 2013, 4(3), 176-185. doi: 10.1007/s13238-013-2084-3 PMID: 23483479
  127. Sp, N.; Kang, D.; Kim, D.; Park, J.; Lee, H.; Kim, H.; Darvin, P.; Park, Y.M.; Yang, Y. Nobiletin inhibits CD36-dependent tumor angiogenesis, migration, invasion, and sphere formation through the Cd36/Stat3/Nf-Kb signaling axis. Nutrients, 2018, 10(6), 772. doi: 10.3390/nu10060772 PMID: 29914089
  128. Teng, Y.; Ross, J.L.; Cowell, J.K. The involvement of JAK-STAT3 in cell motility, invasion, and metastasis. JAK-STAT, 2014, 3(1), e28086. doi: 10.4161/jkst.28086 PMID: 24778926
  129. Mukherjee, A.; Khuda-Bukhsh, A.R. Quercetin down-regulates IL-6/STAT-3 signals to induce mitochondrial-mediated apoptosis in a nonsmall- cell lung-cancer cell line, A549. J. Pharmacopuncture, 2015, 18(1), 19-26. doi: 10.3831/KPI.2015.18.002 PMID: 25830055
  130. Shang, Y.; Cai, X.; Fan, D. Roles of epithelial-mesenchymal transition in cancer drug resistance. Curr. Cancer Drug Targets, 2013, 13(9), 915-929. doi: 10.2174/15680096113136660097 PMID: 24168191
  131. Cai, W.; Yu, D.; Fan, J.; Liang, X.; Jin, H.; Liu, C.; Zhu, M.; Shen, T.; Zhang, R.; Hu, W.; Wei, Q.; Yu, J. Quercetin inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells via the Smad pathway. Drug Des. Devel. Ther., 2018, 12, 4149-4161. doi: 10.2147/DDDT.S185618 PMID: 30584279
  132. Feng, J.; Song, D.; Jiang, S.; Yang, X.; Ding, T.; Zhang, H.; Luo, J.; Liao, J.; Yin, Q. Quercetin restrains TGF-β1-induced epithelial–mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression. Biochem. Biophys. Res. Commun., 2018, 498(1), 132-138. doi: 10.1016/j.bbrc.2018.02.044 PMID: 29425820
  133. Ranganathan, S.; Halagowder, D.; Sivasithambaram, N.D. Quercetin suppresses twist to induce apoptosis in MCF-7 breast cancer cells. PLoS One, 2015, 10(10), e0141370. doi: 10.1371/journal.pone.0141370 PMID: 26491966
  134. Tang, S.N.; Singh, C.; Nall, D.; Meeker, D.; Shankar, S.; Srivastava, R.K. The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J. Mol. Signal., 2010, 5(1), 14. doi: 10.1186/1750-2187-5-14 PMID: 20718984
  135. Sun, S.; Gong, F.; Liu, P.; Miao, Q. Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway. Gene, 2018, 664, 50-57. doi: 10.1016/j.gene.2018.04.045 PMID: 29678660
  136. Shen, X.; Si, Y.; Wang, Z.; Wang, J.; Guo, Y.; Zhang, X. Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling. Int. J. Mol. Med., 2016, 38(2), 619-626. doi: 10.3892/ijmm.2016.2625 PMID: 27278820
  137. Sun, Z.J.; Chen, G.; Hu, X.; Zhang, W.; Liu, Y.; Zhu, L.X.; Zhou, Q.; Zhao, Y.F. Activation of PI3K/Akt/IKK-α/NF-κB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin. Apoptosis, 2010, 15(7), 850-863. doi: 10.1007/s10495-010-0497-5 PMID: 20386985
  138. Szakács, G.; Paterson, J.K.; Ludwig, J.A.; Booth-Genthe, C.; Gottesman, M.M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov., 2006, 5(3), 219-234. doi: 10.1038/nrd1984 PMID: 16518375
  139. Liu, M.; Fu, M.; Yang, X.; Jia, G.; Shi, X.; Ji, J.; Liu, X.; Zhai, G. Paclitaxel and quercetin co-loaded functional mesoporous silica nanoparticles overcoming multidrug resistance in breast cancer. Colloids Surf. B Biointerfaces, 2020, 196, 111284. doi: 10.1016/j.colsurfb.2020.111284 PMID: 32771817
  140. Patra, A.; Satpathy, S.; Shenoy, A.; Bush, J.; Kazi, M.; Hussain, M.D. Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers. Int. J. Nanomedicine, 2018, 13, 2869-2881. doi: 10.2147/IJN.S153094 PMID: 29844670
  141. Daglioglu, C. Enhancing tumor cell response to multidrug resistance with ph-sensitive quercetin and doxorubicin conjugated multifunctional nanoparticles. Colloids Surf. B Biointerfaces, 2017, 156, 175-185. doi: 10.1016/j.colsurfb.2017.05.012 PMID: 28528134
  142. Marques, M.B.; Machado, A.P.; Santos, P.A.; Carrett-Dias, M.; Araújo, G.S.; da Silva Alves, B.; de Oliveira, B.S.; da Silva Júnior, F.M.R.; Dora, C.L.; Cañedo, A.D.; Filgueira, D.M.V.B.; Fernandes e Silva, E.; de Souza Votto, A.P. Anti-MDR effects of quercetin and its nanoemulsion in multidrug-resistant human leukemia cells. Anticancer. Agents Med. Chem., 2021, 21(14), 1911-1920. doi: 10.2174/1871520621999210104200722 PMID: 33397267
  143. Kioka, N.; Hosokawa, N.; Komano, T.; Hirayoshi, K.; Nagate, K.; Ueda, K. Quercetin, a bioflavonoid, inhibits the increase of human multidrug resistance gene (MDR1) expression caused by arsenite. FEBS Lett., 1992, 301(3), 307-309. doi: 10.1016/0014-5793(92)80263-G PMID: 1349537
  144. Scambia, G.; Ranelletti, F.O.; Panici, P.B.; De Vincenzo, R.; Bonanno, G.; Ferrandina, G.; Piantelli, M.; Bussa, S.; Rumi, C.; Cianfriglia, M.; Mancuso, S. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother. Pharmacol., 1994, 34(6), 459-464. doi: 10.1007/BF00685655 PMID: 7923555
  145. Yuan, J.; Wong, I.L.K.; Jiang, T.; Wang, S.W.; Liu, T.; Jin Wen, B.; Chow, L.M.C.; Wan Sheng, B. Synthesis of methylated quercetin derivatives and their reversal activities on P-gp- and BCRP-mediated multidrug resistance tumour cells. Eur. J. Med. Chem., 2012, 54, 413-422. doi: 10.1016/j.ejmech.2012.05.026 PMID: 22743241
  146. Hyun, H.; Moon, J.; Cho, S. Quercetin suppresses CYR61-mediated multidrug resistance in human gastric adenocarcinoma ags cells. Molecules, 2018, 23(2), 209. doi: 10.3390/molecules23020209 PMID: 29364834
  147. Chen, Z.; Huang, C.; Ma, T.; Jiang, L.; Tang, L.; Shi, T.; Zhang, S.; Zhang, L.; Zhu, P.; Li, J.; Shen, A. Reversal effect of quercetin on multidrug resistance via FZD7/β-catenin pathway in hepatocellular carcinoma cells. Phytomedicine, 2018, 43, 37-45. doi: 10.1016/j.phymed.2018.03.040 PMID: 29747752
  148. Yun, H.R.; Jo, Y.H.; Kim, J.; Shin, Y.; Kim, S.S.; Choi, T.G. Roles of autophagy in oxidative stress. Int. J. Mol. Sci., 2020, 21(9), 3289. doi: 10.3390/ijms21093289 PMID: 32384691
  149. Mathew, R.; Karantza-Wadsworth, V.; White, E. Role of autophagy in cancer. Nat. Rev. Cancer, 2007, 7(12), 961-967. doi: 10.1038/nrc2254 PMID: 17972889
  150. Kondo, Y.; Kanzawa, T.; Sawaya, R.; Kondo, S. The role of autophagy in cancer development and response to therapy. Nat. Rev. Cancer, 2005, 5(9), 726-734. doi: 10.1038/nrc1692 PMID: 16148885
  151. Kim, H.; Moon, J.Y.; Ahn, K.S.; Cho, S.K. Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells. Oxid Med Cell Longev, 2013, 2013 doi: 10.1155/2013/596496
  152. Psahoulia, F.H.; Moumtzi, S.; Roberts, M.L.; Sasazuki, T.; Shirasawa, S.; Pintzas, A. Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha- RAS-transformed human colon cells. Carcinogenesis, 2007, 28(5), 1021-1031. doi: 10.1093/carcin/bgl232 PMID: 17148506
  153. Jakubowicz-Gil, J.; Langner, E.; Bądziul, D.; Wertel, I.; Rzeski, W. Silencing of Hsp27 and Hsp72 in glioma cells as a tool for programmed cell death induction upon temozolomide and quercetin treatment. Toxicol. Appl. Pharmacol., 2013, 273(3), 580-589. doi: 10.1016/j.taap.2013.10.003 PMID: 24126416
  154. Calgarotto, A.K.; Maso, V.; Junior, G.C.F.; Nowill, A.E.; Filho, P.L.; Vassallo, J.; Saad, S.T.O. Antitumor activities of quercetin and green tea in xenografts of human leukemia HL60 cells. Sci. Rep., 2018, 8(1), 3459. doi: 10.1038/s41598-018-21516-5 PMID: 29472583
  155. Liu, Y.; Gong, W.; Yang, Z.Y.; Zhou, X.S.; Gong, C.; Zhang, T.R.; Wei, X.; Ma, D.; Ye, F.; Gao, Q.L. Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer. Apoptosis, 2017, 22(4), 544-557. doi: 10.1007/s10495-016-1334-2 PMID: 28188387
  156. Luo, C.; Liu, Y.; Wang, P.; Song, C.; Wang, K.; Dai, L.; Zhang, J.; Ye, H. The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. Biomed. Pharmacother., 2016, 82, 595-605. doi: 10.1016/j.biopha.2016.05.029 PMID: 27470402
  157. Lou, M.; Zhang, L.; Ji, P.; Feng, F.; Liu, J.; Yang, C.; Li, B.; Wang, L. Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuroglioma cells: In vitro and in vivo. Biomed. Pharmacother., 2016, 84, 1-9. doi: 10.1016/j.biopha.2016.08.055 PMID: 27621033
  158. Wang, K.; Liu, R.; Li, J.; Mao, J.; Lei, Y.; Wu, J.; Zeng, J.; Zhang, T.; Wu, H.; Chen, L.; Huang, C.; Wei, Y. Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling. Autophagy, 2011, 7(9), 966-978. doi: 10.4161/auto.7.9.15863 PMID: 21610320
  159. Wu, L.; Li, J.; Liu, T.; Li, S.; Feng, J.; Yu, Q.; Zhang, J.; Chen, J.; Zhou, Y.; Ji, J.; Chen, K.; Mao, Y.; Wang, F.; Dai, W.; Fan, X.; Wu, J.; Guo, C. Quercetin shows anti‐tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway. Cancer Med., 2019, 8(10), 4806-4820. doi: 10.1002/cam4.2388 PMID: 31273958
  160. Jang, E.; Kim, I.Y.; Kim, H.; Lee, D.M.; Seo, D.Y.; Lee, J.A.; Choi, K.S.; Kim, E. Quercetin and chloroquine synergistically kill glioma cells by inducing organelle stress and disrupting Ca2+ homeostasis. Biochem. Pharmacol., 2020, 178, 114098. doi: 10.1016/j.bcp.2020.114098 PMID: 32540484
  161. Bi, Y.; Shen, C.; Li, C.; Liu, Y.; Gao, D.; Shi, C.; Peng, F.; Liu, Z.; Zhao, B.; Zheng, Z.; Wang, X.; Hou, X.; Liu, H.; Wu, J.; Zou, H.; Wang, K.; Zhong, C.; Zhang, J.; Shi, C.; Zhao, S. Inhibition of autophagy induced by quercetin at a late stage enhances cytotoxic effects on glioma cells. Tumour Biol., 2016, 37(3), 3549-3560. doi: 10.1007/s13277-015-4125-4 PMID: 26454746
  162. Tsai, T.F.; Hwang, T.I-S.; Lin, J-F.; Chen, H-E.; Yang, S-C.; Lin, Y-C.; Chou, K-Y.; Chou, K-Y. Suppression of quercetin-induced autophagy enhances cytotoxicity through elevating apoptotic cell death in human bladder cancer cells. Urol. Sci., 2019, 30(2), 58. doi: 10.4103/UROS.UROS_22_18
  163. Chang, J.L.; Chow, J.M.; Chang, J.H.; Wen, Y.C.; Lin, Y.W.; Yang, S.F.; Lee, W.J.; Chien, M.H. Quercetin simultaneously induces G0/G1-phase arrest and caspase-mediated crosstalk between apoptosis and autophagy in human leukemia HL-60 cells. Environ. Toxicol., 2017, 32(7), 1857-1868. doi: 10.1002/tox.22408 PMID: 28251795
  164. Granato, M.; Rizzello, C.; Gilardini Montani, M.S.; Cuomo, L.; Vitillo, M.; Santarelli, R.; Gonnella, R.; D'Orazi, G.; Faggioni, A.; Cirone, M. Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways. J. Nutr. Biochem., 2017, 41, 124-136. doi: 10.1016/j.jnutbio.2016.12.011 PMID: 28092744
  165. Taylor, M.A.; Khathayer, F.; Ray, S.K. Quercetin and sodium butyrate synergistically increase apoptosis in rat C6 and human T98G glioblastoma cells through inhibition of autophagy. Neurochem. Res., 2019, 44(7), 1715-1725. doi: 10.1007/s11064-019-02802-8 PMID: 31011879
  166. Li, J.; Tang, C.; Li, L.; Li, R.; Fan, Y. Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro. J. Neurooncol., 2016, 129(1), 39-45. doi: 10.1007/s11060-016-2149-2 PMID: 27174198
  167. Moon, J.H.; Eo, S.K.; Lee, J.H.; Park, S.Y. Quercetin-induced autophagy flux enhances TRAIL-mediated tumor cell death. Oncol. Rep., 2015, 34(1), 375-381. doi: 10.3892/or.2015.3991 PMID: 25997470
  168. Wang, Z.X.; Ma, J.; Li, X.Y.; Wu, Y.; Shi, H.; Chen, Y.; Lu, G.; Shen, H.M.; Lu, G.D.; Zhou, J. Quercetin induces p53‐independent cancer cell death through lysosome activation by the transcription factor EB and reactive oxygen species‐dependent ferroptosis. Br. J. Pharmacol., 2021, 178(5), 1133-1148. doi: 10.1111/bph.15350 PMID: 33347603
  169. Chung, Y.; Lee, J.; Jung, S.; Lee, Y.; Cho, J.W.; Oh, Y.J. Dysregulated autophagy contributes to caspase-dependent neuronal apoptosis. Cell Death Dis., 2018, 9(12), 1189. doi: 10.1038/s41419-018-1229-y PMID: 30538224
  170. Jung, S.; Jeong, H.; Yu, S.W. Autophagy as a decisive process for cell death. Exp. Mol. Med., 2020, 52(6), 921-930. doi: 10.1038/s12276-020-0455-4 PMID: 32591647
  171. Wu, B.; Zeng, W.; Ouyang, W.; Xu, Q.; Chen, J.; Wang, B.; Zhang, X. Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells. J. Clin. Biochem. Nutr., 2020, 67(2), 137-145. doi: 10.3164/jcbn.19-121 PMID: 33041510
  172. Zhao, Y.; Fan, D.; Zheng, Z.P.; Li, E.T.S.; Chen, F.; Cheng, K.W.; Wang, M. 8-C-(E-phenylethenyl) quercetin from onion/beef soup induces autophagic cell death in colon cancer cells through ERK activation. Mol. Nutr. Food Res., 2017, 61(2), 1600437. doi: 10.1002/mnfr.201600437 PMID: 27670274
  173. Khorsandi, L.; Orazizadeh, M.; Niazvand, F.; Abbaspour, M.R.; Mansouri, E.; Khodadadi, A. Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells. Bratisl. Med. J., 2017, 118(2), 123-128. doi: 10.4149/BLL_2017_025 PMID: 28814095
  174. Collado, M.; Blasco, M.A.; Serrano, M. Cellular senescence in cancer and aging. Cell, 2007, 130(2), 223-233. doi: 10.1016/j.cell.2007.07.003 PMID: 17662938
  175. Ewald, J.A.; Desotelle, J.A.; Wilding, G.; Jarrard, D.F. Therapy-induced senescence in cancer. J. Natl. Cancer Inst., 2010, 102(20), 1536-1546. doi: 10.1093/jnci/djq364 PMID: 20858887
  176. Özsoy, S.; Becer, E.; Kabadayı, H.; Vatansever, H.S.; Yücecan, S. Quercetin-mediated apoptosis and cellular senescence in human colon cancer. Anticancer. Agents Med. Chem., 2020, 20(11), 1387-1396. doi: 10.2174/1871520620666200408082026 PMID: 32268873
  177. Kovacovicova, K.; Skolnaja, M.; Heinmaa, M.; Mistrik, M.; Pata, P.; Pata, I.; Bartek, J.; Vinciguerra, M. Senolytic cocktail Dasatinib + Quercetin (D + Q) does not enhance the efficacy of senescence-inducing chemotherapy in liver cancer. Front. Oncol., 2018, 8, 459. doi: 10.3389/fonc.2018.00459 PMID: 30425964
  178. Zamin, L.L.; Filippi-Chiela, E.C.; Dillenburg-Pilla, P.; Horn, F.; Salbego, C.; Lenz, G. Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells. Cancer Sci., 2009, 100(9), 1655-1662. doi: 10.1111/j.1349-7006.2009.01215.x PMID: 19496785
  179. Klimaszewska-Wiśniewska, A.; Hałas-Wiśniewska, M.; Izdebska, M.; Gagat, M.; Grzanka, A.; Grzanka, D. Antiproliferative and antimetastatic action of quercetin on A549 non-small cell lung cancer cells through its effect on the cytoskeleton. Acta Histochem., 2017, 119(2), 99-112. doi: 10.1016/j.acthis.2016.11.003 PMID: 27887793

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