Effects of Arctigenin in Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma 5-8F Cells

  • Авторлар: Huang D.1, Lu R.2, Cai M.3, Meng J.3, He S.3, Zhang Q.4, Meng W.3
  • Мекемелер:
    1. Department of Otorhinolaryngology-Head and Neck Surgery,, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University
    2. Ophthalmology Department, Affiliated Eye Hospital of Nanjing Medical Universit
    3. Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University
    4. Department of Otorhinolaryngology-Head and Neck Surgery and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University
  • Шығарылым: Том 23, № 10 (2023)
  • Беттер: 1211-1216
  • Бөлім: Oncology
  • URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694291
  • DOI: https://doi.org/10.2174/1871520623666230228155129
  • ID: 694291

Дәйексөз келтіру

Толық мәтін

Аннотация

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharynx.

Objective: Here, we aimed to understand better the molecular basis for arctigenin (ARG)'s ability to promote NPC 5-8F cell invasion.

Methods: We tested the effects of several doses of ARG on 5-8F cells that had been cultured in vitro. We estimated the metabolic activity of cells by The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay. We examined the influence on cell invasion, and migration using Transwell Evaluation. Real-time polymerase chain reaction analysis was used to determine the relative amounts of epidermal growth factor receptor (EGFR), Janus kinase 2 (JAK2) , and transcriptional activator 3 (STAT 3) mRNA expression. Using western blotting, we looked at the level of phosphorylation of specific proteins like EGFR, phosphorylated EGFR, JAK2, and STAT 3.

Results: Our findings revealed that ARG inhibited NPC 5-8F cell development in a dose-and time-dependent manner. The invasiveness and mobility of 5-8F cells were significantly suppressed when ARG was overexpressed in a tumor development model. Expression levels of EGFR, JAK2, and STAT 3 mRNA were considerably low in the experimental group. As a consequence of being treated with ARG, lower levels of EGFR, p-EGFR, p-JAK2, and p-STAT3 expression were observed.

Conclusion: These results suggest that ARG may prevent NPC 5-8F cells from proliferating, migrating, and invading other tissues. There are a few potential molecular pathways, two of which are the inhibition of EGFR phosphorylation and the reduction of levels of phospho-JAK2 and phospho-STAT3.

Авторлар туралы

Dongdong Huang

Department of Otorhinolaryngology-Head and Neck Surgery,, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University

Email: info@benthamscience.net

Rui Lu

Ophthalmology Department, Affiliated Eye Hospital of Nanjing Medical Universit

Email: info@benthamscience.net

Mingjing Cai

Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University

Email: info@benthamscience.net

Jie Meng

Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University

Email: info@benthamscience.net

Shuangba He

Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University

Email: info@benthamscience.net

Qingxiang Zhang

Department of Otorhinolaryngology-Head and Neck Surgery and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University

Email: info@benthamscience.net

Wei Meng

Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Tongren Hospital Affiliated to Medical College of Southeast University

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

Әдебиет тізімі

  1. Cao, S.M.; Simons, M.J.; Qian, C.N. The prevalence and prevention of nasopharyngeal carcinoma in China. Chin. J. Cancer, 2011, 30(2), 114-119. doi: 10.5732/cjc.010.10377 PMID: 21272443
  2. Ma, B.B.Y.; Hui, E.P.; Chan, A.T.C. Systemic approach to improving treatment outcome in nasopharyngeal carcinoma: Current and future directions. Cancer Sci., 2008, 99(7), 1311-1318. doi: 10.1111/j.1349-7006.2008.00836.x PMID: 18498420
  3. Tsai, C.J.; Hofstede, T.M.; Sturgis, E.M.; Garden, A.S.; Lindberg, M.E.; Wei, Q.; Tucker, S.L.; Dong, L. Osteoradionecrosis and radiation dose to the mandible in patients with oropharyngeal cancer. Int. J. Radiat. Oncol. Biol. Phys., 2013, 85(2), 415-420. doi: 10.1016/j.ijrobp.2012.05.032 PMID: 22795804
  4. Wang, H.Y.; Yang, J.S. Studies on the chemical constituents of Arctium lappa L. Yao Xue Xue Bao, 1993, 28(12), 911-917. PMID: 8030415
  5. Shi, H.; Dong, G.; Yan, F.; Zhang, H.; Li, C.; Ma, Q.; Zhang, J.; Ning, Z.; Li, Z.; Dai, J.; Ming, J.; Fang, R.; Si, C.; Xiong, H. Arctigenin ameliorates inflammation by regulating accumulation and functional activity of MDSCs in endotoxin shock. Inflammation, 2018, 41(6), 2090-2100. doi: 10.1007/s10753-018-0852-1 PMID: 30143931
  6. Tang, X.; Zhuang, J.; Chen, J.; Yu, L.; Hu, L.; Jiang, H.; Shen, X. Arctigenin efficiently enhanced sedentary mice treadmill endurance. PLoS One, 2011, 6(8) e24224 doi: 10.1371/journal.pone.0024224 PMID: 21887385
  7. Naoe, A.; Tsuchiya, T.; Kondo, Y.; Uga, N.; Watanabe, S.; Yasui, T.; Hara, F.; Suzuki, T. Arctigenin induces apoptosis in human hepatoblastoma cells. Pediatr. Surg. Int., 2019, 35(6), 723-728. doi: 10.1007/s00383-019-04473-6 PMID: 30891641
  8. Maxwell, T.; Lee, K.; Kim, S.; Nam, K.S. Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells. Int. J. Oncol., 2018, 52(4), 1339-1349. doi: 10.3892/ijo.2018.4271 PMID: 29436614
  9. Huang, Q.; Qin, S.; Yuan, X.; Zhang, L.; Ji, J.; Liu, X.; Ma, W.; Zhang, Y.; Liu, P.; Sun, Z.; Zhang, J.; Liu, Y. Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A. Oncol. Rep., 2017, 38(1), 598-606. doi: 10.3892/or.2017.5667 PMID: 28560452
  10. Zhang, M.; Cai, S.; Zuo, B.; Gong, W.; Tang, Z.; Zhou, D.; Weng, M.; Qin, Y.; Wang, S.; Liu, J.; Ma, F.; Quan, Z. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway. Tumour Biol., 2017, 39(5), 1010428317698359. PMID: 28459363
  11. Jeong, J.B.; Hong, S.C.; Jeong, H.J.; Koo, J.S. Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells. Int. Immunopharmacol., 2011, 11(10), 1573-1577. doi: 10.1016/j.intimp.2011.05.016 PMID: 21621647
  12. Xu, Y.; Lou, Z.; Lee, S.H. Arctigenin represses TGF-β-induced epithelial mesenchymal transition in human lung cancer cells. Biochem. Biophys. Res. Commun., 2017, 493(2), 934-939. doi: 10.1016/j.bbrc.2017.09.117 PMID: 28951214
  13. Hao, Q.; Diaz, T.; Verduzco, A.R.; Magyar, C.E.; Zhong, J.; Elshimali, Y.; Rettig, M.B.; Henning, S.M.; Vadgama, J.V.; Wang, P. Arctigenin inhibits prostate tumor growth in high-fat diet fed mice through dual actions on adipose tissue and tumor. Sci. Rep., 2020, 10(1), 1403. doi: 10.1038/s41598-020-58354-3 PMID: 31996731
  14. Gu, Y.; Qi, C.; Sun, X.; Ma, X.; Zhang, H.; Hu, L.; Yuan, J.; Yu, Q. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism. Biochem. Pharmacol., 2012, 84(4), 468-476. doi: 10.1016/j.bcp.2012.06.002 PMID: 22687625
  15. Susanti, S.; Iwasaki, H.; Inafuku, M.; Taira, N.; Oku, H. Mechanism of arctigenin-mediated specific cytotoxicity against human lung adenocarcinoma cell lines. Phytomedicine, 2013, 21(1), 39-46. doi: 10.1016/j.phymed.2013.08.003 PMID: 24021157
  16. Yang, S.; Ma, J.; Xiao, J.; Lv, X.; Li, X.; Yang, H.; Liu, Y.; Feng, S.; Zhang, Y. Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis. Anatomical Record, 2012, 295(8), 1260-1266.
  17. He, Y.; Fan, Q.; Cai, T.; Huang, W.; Xie, X.; Wen, Y.; Shi, Z. Molecular mechanisms of the action of Arctigenin in cancer. Biomed. Pharmacother., 2018, 108, 403-407.
  18. Sun, Y.; Tan, Y.; Lu, Z.; Li, B.; Sun, C.; Li, T.; Zhao, L.; Liu, Z.; Zhang, G.; Yao, J.; Li, J. Arctigenin inhibits liver cancer tumorigenesis by inhibiting gankyrin expression via C/EBPα and PPARα. Front. Pharmacol., 2018, 9, 268. doi: 10.3389/fphar.2018.00268 PMID: 29636686
  19. Cai, E.; Guo, S.; Yang, L.; Han, M.; Xia, J.; Zhao, Y.; Gao, X.; Wang, Y. Synthesis and antitumour activity of arctigenin amino acid ester derivatives against H22 hepatocellular carcinoma. Nat. Prod. Res., 2018, 32(4), 406-411. doi: 10.1080/14786419.2017.1314279 PMID: 28415847
  20. Baba, Y.; Shigemi, Z.; Hara, N.; Moriguchi, M.; Ikeda, M.; Watanabe, T.; Fujimuro, M. Arctigenin induces the apoptosis of primary effusion lymphoma cells under conditions of glucose deprivation. Int. J. Oncol., 2018, 52(2), 505-517. PMID: 29207179
  21. Yoon, S.B.; Park, H.R. Arctigenin inhibits etoposide resistance in HT-29 colon cancer cells during microenvironmental stress. J. Microbiol. Biotechnol., 2019, 29(4), 571-576. doi: 10.4014/jmb.1901.01061 PMID: 30955254
  22. Hu, X.; Jiao, F.; Zhang, L.; Jiang, Y. Dihydrotanshinone inhibits hepatocellular carcinoma by suppressing the JAK2/STAT3 pathway. Front. Pharmacol., 2021, 12654986 doi: 10.3389/fphar.2021.654986 PMID: 33995073
  23. Lee, H.; Jeong, A.J.; Ye, S.K. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep., 2019, 52(7), 415-423. doi: 10.5483/BMBRep.2019.52.7.152 PMID: 31186087
  24. Yu, H.; Pardoll, D.; Jove, R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat. Rev. Cancer, 2009, 9(11), 798-809. doi: 10.1038/nrc2734 PMID: 19851315
  25. Xu, Q.; Briggs, J.; Park, S.; Niu, G.; Kortylewski, M.; Zhang, S.; Gritsko, T.; Turkson, J.; Kay, H.; Semenza, G.L.; Cheng, J.Q.; Jove, R.; Yu, H. Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene, 2005, 24(36), 5552-5560. doi: 10.1038/sj.onc.1208719 PMID: 16007214
  26. Tam, L.; McGlynn, L.M.; Traynor, P.; Mukherjee, R.; Bartlett, J.M.S.; Edwards, J. Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. Br. J. Cancer, 2007, 97(3), 378-383. doi: 10.1038/sj.bjc.6603871 PMID: 17595657
  27. Mora, L.B.; Buettner, R.; Seigne, J.; Diaz, J.; Ahmad, N.; Garcia, R.; Bowman, T.; Falcone, R.; Fairclough, R.; Cantor, A.; Muro-Cacho, C.; Livingston, S.; Karras, J.; Pow-Sang, J.; Jove, R. Constitutive activation of Stat3 in human prostate tumors and cell lines: Direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res., 2002, 62(22), 6659-6666. PMID: 12438264
  28. Kanda, N.; Seno, H.; Konda, Y.; Marusawa, H.; Kanai, M.; Nakajima, T.; Kawashima, T.; Nanakin, A.; Sawabu, T.; Uenoyama, Y.; Sekikawa, A.; Kawada, M.; Suzuki, K.; Kayahara, T.; Fukui, H.; Sawada, M.; Chiba, T. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene, 2004, 23(28), 4921-4929. doi: 10.1038/sj.onc.1207606 PMID: 15077160
  29. Song, L.; Turkson, J.; Karras, J.G.; Jove, R.; Haura, E.B. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene, 2003, 22(27), 4150-4165. doi: 10.1038/sj.onc.1206479 PMID: 12833138
  30. Chen, C-L.; Hsieh, F-C.; Lieblein, J.C.; Brown, J.; Chan, C.; Wallace, J.A.; Cheng, G.; Hall, B.M.; Lin, J. Stat3 activation in human endometrial and cervical cancers. Br. J. Cancer, 2007, 96(4), 591-599. doi: 10.1038/sj.bjc.6603597 PMID: 17311011
  31. Huynh, J.; Chand, A.; Gough, D.; Ernst, M. Therapeutically exploiting STAT3 activity in cancer using tissue repair as a road map. Nat. Rev. Cancer, 2019, 19(2), 82-96. doi: 10.1038/s41568-018-0090-8 PMID: 30578415
  32. Lu, Z.; Chang, L.; Zhou, H.; Liu, X.; Li, Y.; Mi, T.; Tong, D. Arctigenin attenuates tumor metastasis through inhibiting epithelial-mesenchymal transition in hepatocellular carcinoma via suppressing GSK3β-dependent Wnt/β-catenin signaling pathway In Vivo and In Vitro. Front. Pharmacol., 2019, 10, 937. doi: 10.3389/fphar.2019.00937 PMID: 31555129
  33. Jiang, Y.; Liu, J.; Hong, W.; Fei, X.; Liu, R. Arctigenin inhibits glioblastoma proliferation through the AKT/mTOR pathway and induces autophagy. Bio. Med. Res. Int., 2020, 20203542613 doi: 10.1155/2020/3542613 PMID: 33015162

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