Anticancer Properties Against Select Cancer Cell Lines and Metabolomics Analysis of Tender Coconut Water


Дәйексөз келтіру

Толық мәтін

Аннотация

Background:Tender Coconut Water (TCW) is a nutrient-rich dietary supplement that contains bioactive secondary metabolites and phytohormones with anti-oxidative and anti-inflammatory properties. Studies on TCW’s anti-cancer properties are limited and the mechanism of its anti-cancer effects have not been defined.

Objective:In the present study, we investigate TCW for its anti-cancer properties and, using untargeted metabolomics, we identify components form TCW with potential anti-cancer activity.

Methodology:Cell viability assay, BrdU incorporation assay, soft-agar assay, flow-cytometery, and Western blotting were used to analyze TCW’s anticancer properties and to identify mechanism of action. Liquid chromatography- Tandem Mass Spectroscopy (LC-MS/MS) was used to identify TCW components.

Results:TCW decreased the viability and anchorage-independent growth of HepG2 hepatocellular carcinoma (HCC) cells and caused S-phase cell cycle arrest. TCW inhibited AKT and ERK phosphorylation leading to reduced ZEB1 protein, increased E-cadherin, and reduced N-cadherin protein expression in HepG2 cells, thus reversing the ‘epithelial-to-mesenchymal’ (EMT) transition. TCW also decreased the viability of Hep3B hepatoma, HCT-15 colon, MCF-7 and T47D luminal A breast cancer (BC) and MDA-MB-231 and MDA-MB-468 triplenegative BC cells. Importantly, TCW did not inhibit the viability of MCF-10A normal breast epithelial cells. Untargeted metabolomics analysis of TCW identified 271 metabolites, primarily lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic oxygen compounds. We demonstrate that three components from TCW: 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, iondole-3-carbox aldehyde and caffeic acid inhibit the growth of cancer cells.

Conclusion:TCW and its components exhibit anti-cancer effects. TCW inhibits the viability of HepG2 hepatocellular carcinoma cells by reversing the EMT process through inhibition of AKT and ERK signalling.

Авторлар туралы

Jaganathan Lakshmanan

Dr. Hiram C. Polk, Jr., MD, Department of Surgery, and Price Institute of Surgical Research, School of Medicine, University of Louisville

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Vaitheesh Jaganathan

Dr. Hiram C. Polk, Jr., MD, Department of Surgery, and Price Institute of Surgical Research, School of Medicine, University of Louisville

Email: info@benthamscience.net

Boachun Zhang

Dr. Hiram C. Polk, Jr., MD, Department of Surgery, and Price Institute of Surgical Research, School of Medicine, University of Louisville

Email: info@benthamscience.net

Grace Werner

Dr. Hiram C. Polk, Jr., MD, Department of Surgery, and Price Institute of Surgical Research, School of Medicine, University of Louisville

Email: info@benthamscience.net

Tyler Allen

Dr. Hiram C. Polk, Jr., MD, Department of Surgery, and Price Institute of Surgical Research, School of Medicine, University of Louisville

Email: info@benthamscience.net

David Schultz

Department of Biology, School of Medicine, University of Louisville

Email: info@benthamscience.net

Carolyn Klinge

Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville

Email: info@benthamscience.net

Brian Harbrecht

Dr. Hiram C. Polk, Jr., MD, Department of Surgery, and Price Institute of Surgical Research, School of Medicine, University of Louisville

Email: info@benthamscience.net

Әдебиет тізімі

  1. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424. doi: 10.3322/caac.21492 PMID: 30207593
  2. Ferlay, J.; Colombet, M.; Soerjomataram, I.; Parkin, D.M.; Pineros, M.; Znaor, A.; Bray, F. Cancer statistics for the year 2020: An overview. Int. J. Cancer, 2021, 149(4), 778-789. doi: 10.1002/ijc.33588 PMID: 33818764
  3. Siegel, R.L.; Giaquinto, A.N.; Jemal, A. Cancer statistics, 2024. CA Cancer J. Clin., 2024, 74(1), 12-49. doi: 10.3322/caac.21820 PMID: 38230766
  4. Choudhari, A.S.; Mandave, P.C.; Deshpande, M.; Ranjekar, P.; Prakash, O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Front. Pharmacol., 2020, 10, 1614. doi: 10.3389/fphar.2019.01614 PMID: 32116665
  5. Seca, A.; Pinto, D. Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. Int. J. Mol. Sci., 2018, 19(1), 263. doi: 10.3390/ijms19010263 PMID: 29337925
  6. Demain, A.L.; Vaishnav, P. Natural products for cancer chemotherapy. Microb. Biotechnol., 2011, 4(6), 687-699. doi: 10.1111/j.1751-7915.2010.00221.x PMID: 21375717
  7. Asma, S.T.; Acaroz, U.; Imre, K.; Morar, A.; Shah, S.R.A.; Hussain, S.Z.; Arslan-Acaroz, D.; Demirbas, H.; Hajrulai-Musliu, Z.; Istanbullugil, F.R.; Soleimanzadeh, A.; Morozov, D.; Zhu, K.; Herman, V.; Ayad, A.; Athanassiou, C.; Ince, S. Natural products/bioactive compounds as a source of anticancer drugs. Cancers (Basel), 2022, 14(24), 6203. doi: 10.3390/cancers14246203 PMID: 36551687
  8. Naeem, A.; Hu, P.; Yang, M.; Zhang, J.; Liu, Y.; Zhu, W.; Zheng, Q. Natural products as anticancer agents: Current status and future perspectives. Molecules, 2022, 27(23), 8367. doi: 10.3390/molecules27238367 PMID: 36500466
  9. Talib, W.H.; Daoud, S.; Mahmod, A.I.; Hamed, R.A.; Awajan, D.; Abuarab, S.F.; Odeh, L.H.; Khater, S.; Al Kury, L.T. Plants as a source of anticancer agents: From bench to bedside. Molecules, 2022, 27(15), 4818. doi: 10.3390/molecules27154818 PMID: 35956766
  10. Hashem, S.; Ali, T.A.; Akhtar, S.; Nisar, S.; Sageena, G.; Ali, S.; Al-Mannai, S.; Therachiyil, L.; Mir, R.; Elfaki, I.; Mir, M.M.; Jamal, F.; Masoodi, T.; Uddin, S.; Singh, M.; Haris, M.; Macha, M.; Bhat, A.A. Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents. Biomed. Pharmacother., 2022, 150, 113054. doi: 10.1016/j.biopha.2022.113054 PMID: 35658225
  11. Chunarkar-Patil, P.; Kaleem, M.; Mishra, R.; Ray, S.; Ahmad, A.; Verma, D.; Bhayye, S.; Dubey, R.; Singh, H.; Kumar, S. Anticancer drug discovery based on natural products: From computational approaches to clinical studies. Biomed., 2024, 12(1), 201. doi: 10.3390/biomedicines12010201 PMID: 38255306
  12. Grover, P.; Thakur, K.; Bhardwaj, M.; Mehta, L.; Raina, S.N.; Rajpal, V.R. Phytotherapeutics in cancer: From potential drug candidates to clinical translation. Curr. Top. Med. Chem., 2024, 24(12), 1050-1074. doi: 10.2174/0115680266282518231231075311 PMID: 38279745
  13. Kumar, M.; Gupta, S.; Kalia, K.; Kumar, D. Role of phytoconstituents in cancer treatment: A review. Rec. Adv. Food Nutr. Agric., 2024, 15(2), 115-137. doi: 10.2174/012772574X274566231220051254 PMID: 38369892
  14. Yuan, C.; Zhang, W.; Wang, J.; Huang, C.; Shu, B.; Liang, Q.; Huang, T.; Wang, J.; Shi, Q.; Tang, D.; Wang, Y. Chinese Medicine Phenomics (Chinmedphenomics): Personalized, Precise and Promising. Phenomics, 2022, 2(6), 383-388. doi: 10.1007/s43657-022-00074-x PMID: 36939806
  15. Zhang, N.; Xiao, X. Integrative medicine in the era of cancer immunotherapy: Challenges and opportunities. J. Integr. Med., 2021, 19(4), 291-294. doi: 10.1016/j.joim.2021.03.005 PMID: 33814325
  16. Yong, J.W.H.; Ge, L.; Ng, Y.F.; Tan, S.N. The chemical composition and biological properties of coconut (Cocos nucifera L.) water. Molecules, 2009, 14(12), 5144-5164. doi: 10.3390/molecules14125144 PMID: 20032881
  17. Ge, L.; Yong, J.; Tan, S.; Yang, X.; Ong, E. Analysis of some cytokinins in coconut (Cocos nucifera L.) water by micellar electrokinetic capillary chromatography after solid-phase extraction. J. Chromatogr. A, 2004, 1048(1), 119-126. doi: 10.1016/S0021-9673(04)01186-0 PMID: 15453426
  18. Tan, S.; Yong, J.; Ge, L. Analyses of phytohormones in coconut (Cocos nucifera L.) water using capillary electrophoresis-tandem mass spectrometry. Chromatography (Basel), 2014, 1(4), 211-226. doi: 10.3390/chromatography1040211
  19. Prabhu, S.; Dennison, S.R.; Mura, M.; Lea, R.W.; Snape, T.J.; Harris, F. Cn‐AMP2 from green coconut water is an anionic anticancer peptide. J. Pept. Sci., 2014, 20(12), 909-915. doi: 10.1002/psc.2684 PMID: 5234689
  20. Mahayothee, B.; Koomyart, I.; Khuwijitjaru, P.; Siriwongwilaichat, P.; Nagle, M.; Müller, J. Phenolic compounds, antioxidant activity, and medium chain fatty acids profiles of coconut water and meat at different maturity stages. Int. J. Food Prop., 2016, 19(9), 2041-2051. doi: 10.1080/10942912.2015.1099042
  21. DebMandal, M.; Mandal, S. Coconut (Cocos nucifera L.: Arecaceae): In health promotion and disease prevention. Asian Pac. J. Trop. Med., 2011, 4(3), 241-247. doi: 10.1016/S1995-7645(11)60078-3 PMID: 21771462
  22. Saat, M.; Singh, R.; Sirisinghe, R.G.; Nawawi, M. Rehydration after exercise with fresh young coconut water, carbohydrate-electrolyte beverage and plain water. J. Physiol. Anthropol. Appl. Human Sci., 2002, 21(2), 93-104. doi: 10.2114/jpa.21.93 PMID: 12056182
  23. Kalman, D.S.; Feldman, S.; Krieger, D.R.; Bloomer, R.J. Comparison of coconut water and a carbohydrate-electrolyte sport drink on measures of hydration and physical performance in exercise-trained men. J. Int. Soc. Sports Nutr., 2012, 9(1), 1. doi: 10.1186/1550-2783-9-1 PMID: 22257640
  24. Campbell-Falck, D.; Thomas, T.; Falck, T.M.; Tutuo, N.; Clem, K. The intravenous use of coconut water. Am. J. Emerg. Med., 2000, 18(1), 108-111. doi: 10.1016/S0735-6757(00)90062-7 PMID: 10674546
  25. Souza, B.D.M.; Lückemeyer, D.D.; Reyes-Carmona, J.F.; Felippe, W.T.; Simões, C.M.O.; Felippe, M.C.S. Viability of human periodontal ligament fibroblasts in milk, Hank’s balanced salt solution and coconut water as storage media. Int. Endod. J., 2011, 44(2), 111-115. doi: 10.1111/j.1365-2591.2010.01809.x PMID: 21083571
  26. Lakshmanan, J.; Zhang, B.; Wright, K.; Motameni, A.T.; Herbst, J.L.; Harbrecht, B.G. Tender coconut water protects mice from ischemia-reperfusion-mediated liver injury and secondary lung injury. Shock, 2021, 56(5), 762-772. doi: 10.1097/SHK.0000000000001770 PMID: 34652342
  27. Lakshmanan, J.; Zhang, B.; Wright, K.; Motameni, A.T.; Jaganathan, V.L.; Schultz, D.J.; Klinge, C.M.; Harbrecht, B.G. Tender coconut water suppresses hepatic inflammation by activating AKT and JNK signaling pathways in an in vitro model of sepsis. J. Funct. Foods, 2020, 64, 103637. doi: 10.1016/j.jff.2019.103637 PMID: 32863888
  28. Ge, L.; Yong, J.W.H.; Goh, N.K.; Chia, L.S.; Tan, S.N.; Ong, E.S. Identification of kinetin and kinetin riboside in coconut (Cocos nucifera L.) water using a combined approach of liquid chromatography–tandem mass spectrometry, high performance liquid chromatography and capillary electrophoresis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2005, 829(1-2), 26-34. doi: 10.1016/j.jchromb.2005.09.026 PMID: 16216563
  29. Chang, C.L.; Wu, R.T. Quantification of (+)-catechin and (−)-epicatechin in coconut water by LC–MS. Food Chem., 2011, 126(2), 710-717. doi: 10.1016/j.foodchem.2010.11.034
  30. Cabello, C.M.; Bair, W.B., III; Ley, S.; Lamore, S.D.; Azimian, S.; Wondrak, G.T. The experimental chemotherapeutic N6-furfuryladenosine (kinetin-riboside) induces rapid ATP depletion, genotoxic stress, and CDKN1A (p21) upregulation in human cancer cell lines. Biochem. Pharmacol., 2009, 77(7), 1125-1138. doi: 10.1016/j.bcp.2008.12.002 PMID: 19186174
  31. Casati, S.; Ottria, R.; Baldoli, E.; Lopez, E.; Maier, J.A.M.; Ciuffreda, P. Effects of cytokinins, cytokinin ribosides and their analogs on the viability of normal and neoplastic human cells. Anticancer Res., 2011, 31(10), 3401-3406. PMID: 21965753
  32. Sharma, E.; Attri, D.C.; Sati, P.; Dhyani, P.; Szopa, A.; Sharifi-Rad, J.; Hano, C.; Calina, D.; Cho, W.C. Recent updates on anticancer mechanisms of polyphenols. Front. Cell Dev. Biol., 2022, 10, 1005910. doi: 10.3389/fcell.2022.1005910 PMID: 36247004
  33. Kirszberg, C.; Esquenazi, D.; Alviano, C.S.; Rumjanek, V.M. The effect of a catechin‐rich extract of Cocos nucifera on lymphocytes proliferation. Phytother. Res., 2003, 17(9), 1054-1058. doi: 10.1002/ptr.1297 PMID: 14595586
  34. Prades, A.; Dornier, M.; Diop, N.; Pain, J-P. Coconut water uses, composition and properties: A review. Fruits, 2012, 67(2), 87-107. doi: 10.1051/fruits/2012002
  35. Chen, W.; Zhang, G.; Chen, W.; Zhong, Q.; Chen, H. Metabolomic profiling of matured coconut water during post-harvest storage revealed discrimination and distinct changes in metabolites. RSC Advances, 2018, 8(55), 31396-31405. doi: 10.1039/C8RA04213F PMID: 35548195
  36. Zhang, Y.; Chen, W.; Chen, H.; Zhong, Q.; Yun, Y.; Chen, W. Metabolomics analysis of the deterioration mechanism and storage time limit of tender coconut water during storage. Foods, 2020, 9(1), 46-46. doi: 10.3390/foods9010046 PMID: 31947875
  37. Alseekh, S.; Fernie, A.R. Metabolomics 20 years on: what have we learned and what hurdles remain? Plant J., 2018, 94(6), 933-942. doi: 10.1111/tpj.13950 PMID: 29734513
  38. Ghalehno, A.; Boustan, A.; Abdi, H.; Aganj, Z.; Mosaffa, F.; Jamialahmadi, K. The potential for natural products to overcome cancer drug resistance by modulation of epithelial-mesenchymal transition. Nutr. Cancer, 2022, 74(8), 2686-2712. doi: 10.1080/01635581.2021.2022169 PMID: 34994266
  39. Bahrami, A.; Majeed, M.; Sahebkar, A. Curcumin: A potent agent to reverse epithelial-to-mesenchymal transition. Cell Oncol. (Dordr.), 2019, 42, 405-421. doi: 10.1007/s13402-019-00442-2 PMID: 30980365
  40. Lee, S.; Choi, E.J.; Cho, E.J.; Lee, Y.B.; Lee, J.H.; Yu, S.J.; Yoon, J.H.; Kim, Y.J. Inhibition of PI3K/Akt signaling suppresses epithelial-to-mesenchymal transition in hepatocellular carcinoma through the Snail/GSK-3/beta-catenin pathway. Clin. Mol. Hepatol., 2020, 26(4), 529-539. doi: 10.3350/cmh.2019.0056n PMID: 32829570
  41. Yang, Y.; Li, Y.; Wang, K.; Wang, Y.; Yin, W.; Li, L. P38/NF-κB/snail pathway is involved in caffeic acid-induced inhibition of cancer stem cells-like properties and migratory capacity in malignant human keratinocyte. PLoS One, 2013, 8(3), e58915. doi: 10.1371/journal.pone.0058915 PMID: 23516577
  42. Yilmaz, M.; Christofori, G. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev., 28(1-2), 15-33. doi: 10.1007/s10555-008-9169-0 PMID: 19169796
  43. Perez-Oquendo, M.; Gibbons, D.L. Regulation of ZEB1 function and molecular associations in tumor Progression and metastasis. Cancers (Basel), 2022, 14(8), 1864. doi: 10.3390/cancers14081864 PMID: 35454770
  44. Xu, W.; Yang, Z.; Lu, N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adhes. Migr., 2015, 9(4), 317-324. doi: 10.1080/19336918.2015.1016686 PMID: 26241004
  45. Torii, S.; Yamamoto, T.; Tsuchiya, Y.; Nishida, E. ERK MAP kinase in G cell cycle progression and cancer. Cancer Sci., 2006, 97(8), 697-701. doi: 10.1111/j.1349-7006.2006.00244.x PMID: 16800820
  46. Calvisi, D.F.; Ladu, S.; Gorden, A.; Farina, M.; Conner, E.A.; Lee, J.S.; Factor, V.M.; Thorgeirsson, S.S. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology, 2006, 130(4), 1117-1128. doi: 10.1053/j.gastro.2006.01.006 PMID: 16618406
  47. Chiu, L-Y.; Hsin, I-L.; Yang, T-Y.; Sung, W-W.; Chi, J-Y.; Chang, J.T.; Ko, J-L.; Sheu, G-T. The ERK–ZEB1 pathway mediates epithelial–mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids. Oncogene, 2017, 36(2), 242-253. doi: 10.1038/onc.2016.195 PMID: 27270426
  48. Zhang, A.; Lakshmanan, J.; Motameni, A.; Harbrecht, B.G. MicroRNA-203 suppresses proliferation in liver cancer associated with PIK3CA, p38 MAPK, c-Jun, and GSK3 signaling. Mol. Cell. Biochem., 2018, 441(1-2), 89-98. doi: 10.1007/s11010-017-3176-9 PMID: 28887744
  49. Schultz, D.J.; Muluhngwi, P.; Alizadeh-Rad, N.; Green, M.A.; Rouchka, E.C.; Waigel, S.J.; Klinge, C.M. Genome-wide miRNA response to anacardic acid in breast cancer cells. PLoS One, 2017, 12(9), e0184471-e0184471. doi: 10.1371/journal.pone.0184471 PMID: 28886127
  50. Crane, A.M.; Bhattacharya, S.K. The use of bromodeoxyuridine incorporation assays to assess corneal stem cell proliferation. Methods Mol. Biol., 2013, 1014, 65-70. doi: 10.1007/978-1-62703-432-6_4 PMID: 23690005
  51. Borowicz, S.; Van Scoyk, M.; Avasarala, S.; Karuppusamy, R.M.K.; Tauler, J.; Bikkavilli, R.K.; Winn, R.A. The soft agar colony formation assay. J. Vis. Exp., 2014, (92), e51998. doi: 10.3791/51998 PMID: 25408172
  52. Lakshmanan, J.; Zhang, B.; Nweze, I.C.; Du, Y.; Harbrecht, B.G. Glycogen synthase kinase 3 regulates IL-1β mediated iNOS expression in hepatocytes by down-regulating c-Jun. J. Cell. Biochem., 2015, 116(1), 133-141. doi: 10.1002/jcb.24951 PMID: 25160751
  53. Ardalani, H.; Vidkjær, N.H.; Kryger, P.; Fiehn, O.; Fomsgaard, I.S. Metabolomics unveils the influence of dietary phytochemicals on residual pesticide concentrations in honey bees. Environ. Int., 2021, 152, 106503. doi: 10.1016/j.envint.2021.106503 PMID: 33756430
  54. Bonini, P.; Kind, T.; Tsugawa, H.; Barupal, D.K.; Fiehn, O. Retip: Retention time prediction for compound annotation in untargeted metabolomics. Anal. Chem., 2020, 92(11), 7515-7522. doi: 10.1021/acs.analchem.9b05765 PMID: 32390414
  55. Wang, L-H. Molecular signaling regulating anchorage-independent growth of cancer cells. Mt. Sinai J. Med., 2004, 71(6), 361-367. PMID: 15592654
  56. David-Pfeuty, T. The flexible evolutionary anchorage-dependent Pardee’s restriction point of mammalian cells: how its deregulation may lead to cancer. Biochim. Biophys. Acta, 2006, 1765(1), 38-66. PMID: 16219425
  57. Schmalhofer, O.; Brabletz, S.; Brabletz, T. E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev., 2009, 28(1-2), 151-166. doi: 10.1007/s10555-008-9179-y PMID: 19153669
  58. Soule, H.D.; Maloney, T.M.; Wolman, S.R.; Peterson, W.D., Jr; Brenz, R.; McGrath, C.M.; Russo, J.; Pauley, R.J.; Jones, R.F.; Brooks, S.C. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res., 1990, 50(18), 6075-6086. PMID: 1975513
  59. Feunang, Y.; Eisner, R.; Knox, C.; Chepelev, L.; Hastings, J.; Owen, G.; Fahy, E.; Steinbeck, C.; Subramanian, S.; Bolton, E.; Greiner, R.; Wishart, D.S. ClassyFire: automated chemical classification with a comprehensive, computable taxonomy. J. Cheminform., 2016, 8(1), 61. doi: 10.1186/s13321-016-0174-y PMID: 27867422
  60. Appaiah, P.; Sunil, L.; Kumar, P.K.P.; Krishna, A.G.G. Physico-chemical characteristics and stability aspects of coconut water and kernel at different stages of maturity. J. Food Sci. Technol., 2015, 52(8), 5196-5203. doi: 10.1007/s13197-014-1559-4 PMID: 26243942
  61. Amawi, H.; Ashby, C.R., Jr; Tiwari, A.K. Cancer chemoprevention through dietary flavonoids: what’s limiting? Chin. J. Cancer, 2017, 36(1), 50. doi: 10.1186/s40880-017-0217-4 PMID: 28629389
  62. Voller, J.; Béres, T.; Zatloukal, M.; Džubák, P.; Hajdúch, M.; Doležal, K.; Schmülling, T.; Miroslav, S. Anti-cancer activities of cytokinin ribosides. Phytochem. Rev., 2019, 18(4), 1101-1113. doi: 10.1007/s11101-019-09620-4
  63. Garcia-Lezana, T.; Lopez-Canovas, J.L.; Villanueva, A. Signaling pathways in hepatocellular carcinoma. Adv. Cancer Res., 2021, 149, 63-101. doi: 10.1016/bs.acr.2020.10.002 PMID: 33579428
  64. Fatima, I.; El-Ayachi, I.; Taotao, L.; Lillo, M.A.; Krutilina, R.; Seagroves, T.N.; Radaszkiewicz, T.W.; Hutnan, M.; Bryja, V.; Krum, S.A.; Rivas, F.; Miranda-Carboni, G.A. The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer. PLoS One, 2017, 12(12), e0189864. doi: 10.1371/journal.pone.0189864 PMID: 29281678
  65. Lou, W.; Chen, Y.; Zhu, K.; Deng, H.; Wu, T.; Wang, J.; Polyphyllin, I. Polyphyllin I overcomes EMT-associated resistance to erlotinib in lung cancer cells via IL-6/STAT3 pathway inhibition. Biol. Pharm. Bull., 2017, 40(8), 1306-1313. doi: 10.1248/bpb.b17-00271 PMID: 28515374
  66. Lee, G.A.; Hwang, K.A.; Choi, K.C. Roles of dietary phytoestrogens on the regulation of epithelial-mesenchymal transition in diverse cancer metastasis. Toxins (Basel), 2016, 8(6), 162. doi: 10.3390/toxins8060162 PMID: 27231938
  67. Qiu, G.H.; Xie, X.; Xu, F.; Shi, X.; Wang, Y.; Deng, L. Distinctive pharmacological differences between liver cancer cell lines HepG2 and Hep3B. Cytotechnology, 2015, 67(1), 1-12. doi: 10.1007/s10616-014-9761-9 PMID: 25002206
  68. Bressac, B.; Galvin, K.M.; Liang, T.J.; Isselbacher, K.J.; Wands, J.R.; Ozturk, M. Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA, 1990, 87(5), 1973-1977. doi: 10.1073/pnas.87.5.1973 PMID: 2155427
  69. Slany, A.; Haudek, V.J.; Zwickl, H.; Gundacker, N.C.; Grusch, M.; Weiss, T.S.; Seir, K.; Rodgarkia-Dara, C.; Hellerbrand, C.; Gerner, C. Cell characterization by proteome profiling applied to primary hepatocytes and hepatocyte cell lines Hep-G2 and Hep-3B. J. Proteome Res., 2010, 9(1), 6-21. doi: 10.1021/pr900057t PMID: 19678649
  70. Clement, E.; Inuzuka, H.; Nihira, N.T.; Wei, W.; Toker, A. Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors. Sci. Signal., 2018, 11(521), eaao3810. doi: 10.1126/scisignal.aao3810 PMID: 29535262
  71. Cunha, A.G.; Filho, E.G.; Silva, L.M.A.; Ribeiro, P.R.V.; Rodrigues, T.H.S.; Brito, E.S.; Miranda, M.R.A. Chemical composition of thermally processed coconut water evaluated by GC–MS, UPLC-HRMS, and NMR. Food Chem., 2020, 324, 126874-126874. doi: 10.1016/j.foodchem.2020.126874 PMID: 32353658
  72. Kim, K.H.; Moon, E.; Kim, H.K.; Oh, J.Y.; Kim, S.Y.; Choi, S.U.; Lee, K.R. Phenolic constituents from the rhizomes of Acorus gramineus and their biological evaluation on antitumor and anti-inflammatory activities. Bioorg. Med. Chem. Lett., 2012, 22(19), 6155-6159. doi: 10.1016/j.bmcl.2012.08.016 PMID: 22951040
  73. Mohamed, A.; Ashour, E.S.E.; Rainer, E. RuAngelie, E.; Peter, P. Indole alkaloid from the red sea sponge Hytitos erectus. ARKIVOC, 2007, XV, 225-231.
  74. Mirzaei, S.; Gholami, M.H.; Zabolian, A.; Saleki, H.; Farahani, M.V.; Hamzehlou, S.; Far, F.B.; Sharifzadeh, S.O.; Samarghandian, S.; Khan, H.; Aref, A.R.; Ashrafizadeh, M.; Zarrabi, A.; Sethi, G. Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer. Pharmacol. Res., 2021, 171, 105759. doi: 10.1016/j.phrs.2021.105759 PMID: 34245864
  75. Morré, D.J.; Morré, D.M.; Sun, H.; Cooper, R.; Chang, J.; Janle, E.M. Tea catechin synergies in inhibition of cancer cell proliferation and of a cancer specific cell surface oxidase (ECTO-NOX). Pharmacol. Toxicol., 2003, 92(5), 234-241. doi: 10.1034/j.1600-0773.2003.920506.x PMID: 12753411
  76. Kuzuhara, T.; Suganuma, M.; Fujiki, H. Green tea catechin as a chemical chaperone in cancer prevention. Cancer Lett., 2008, 261(1), 12-20. doi: 10.1016/j.canlet.2007.10.037 PMID: 18068893
  77. Voller, J.; Zatloukal, M.; Lenobel, R.; Doležal, K.; Béreš, T.; Kryštof, V.; Spíchal, L.; Niemann, P.; Džubák, P.; Hajdúch, M.; Strnad, M. Anticancer activity of natural cytokinins: A structure–activity relationship study. Phytochemistry, 2010, 71(11-12), 1350-1359. doi: 10.1016/j.phytochem.2010.04.018 PMID: 20553699
  78. Habtemariam, S.; Lentini, G. Plant-derived anticancer agents: Lessons from the pharmacology of geniposide and its aglycone, genipin. Biomed., 2018, 6(2), 39. doi: 10.3390/biomedicines6020039 PMID: 29587429
  79. Kim, N.Y.; Ha, I.J.; Um, J.Y.; Kumar, A.P.; Sethi, G.; Ahn, K.S. Loganic acid regulates the transition between epithelial and mesenchymal-like phenotypes by alleviating MnSOD expression in hepatocellular carcinoma cells. Life Sci., 2023, 317, 121458. doi: 10.1016/j.lfs.2023.121458 PMID: 36731649
  80. Tintelnot, J.; Xu, Y.; Lesker, T.R.; Schönlein, M.; Konczalla, L.; Giannou, A.D.; Pelczar, P.; Kylies, D.; Puelles, V.G.; Bielecka, A.A.; Peschka, M.; Cortesi, F.; Riecken, K.; Jung, M.; Amend, L.; Bröring, T.S.; Trajkovic-Arsic, M.; Siveke, J.T.; Renné, T.; Zhang, D.; Boeck, S.; Strowig, T.; Uzunoglu, F.G.; Güngör, C.; Stein, A.; Izbicki, J.R.; Bokemeyer, C.; Sinn, M.; Kimmelman, A.C.; Huber, S.; Gagliani, N. Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer. Nature, 2023, 615(7950), 168-174. doi: 10.1038/s41586-023-05728-y PMID: 36813961
  81. Santos, R.A.; Pessoa, H.R.; Daleprane, J.B.; De Faria Lopes, G.P.; da Costa, D.C.F. Comparative anticancer potential of green tea extract and epigallocatechin-3-gallate on breast cancer spheroids. Foods, 2023, 13(1), 64. doi: 10.3390/foods13010064 PMID: 38201092
  82. Tapadar, P.; Pal, A.; Ghosal, N.; Dutta, S.; Pal, R. Reactive oxygen species–dependent upregulation of death receptor, tumor necrosis factor receptor 1, is responsible for theophylline-mediated cytotoxicity in MDA-MB-231 breast cancer cells. Anticancer Drugs, 2022, 33(8), 731-740. doi: 10.1097/CAD.0000000000001322 PMID: 35946512
  83. Efferth, T.; Koch, E. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr. Drug Targets, 2011, 12(1), 122-132. doi: 10.2174/138945011793591626 PMID: 20735354

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