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Glaucocalyxin A Activates FasL and Induces Apoptosis Through Activation of the JNK Pathway in Human Breast Cancer Cells

  • Li, Mei (Department of Pharmacology and Laboratory of Aging and Nervous Diseases, School of Pharmaceutical Science, Soochow University) ;
  • Jiang, Xiao-Gang (Department of Pharmacology, Medical College, Soochow University) ;
  • Gu, Zhen-Lun (Suzhou Institute of Chinese Materia Medica) ;
  • Zhang, Zu-Bin (Department of Pharmacology, Medical College, Soochow University)
  • 발행 : 2013.10.30

초록

This study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively. Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as $1{\mu}M$ in MCF-7 and $4{\mu}M$ in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.

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참고문헌

  1. Antonsson BJ, Martinou C (2000). The Bcl-2 protein family. Exp Cell Res, 256, 50-7. https://doi.org/10.1006/excr.2000.4839
  2. Bishayee A, Ahmed S, Brankov M, Perloff N (2011). Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci, 16, 980-96. https://doi.org/10.2741/3730
  3. Chatzistamou I, Schally AV, Sun B, et al (2000). Inhibition of growth of OV-1063 human epithelial ovarian cancers and c- jun and c- fos oncogene expression by bombesin antagonists. Br J Cancer, 83, 906-13. https://doi.org/10.1054/bjoc.2000.1374
  4. Chen KC, Chang LS (2010). Notexin upregulates Fas and FasL protein expression of human neuroblastoma SK-N-SH cells through p38 MAPK/ATF-2 and JNK/c-Jun pathways. Toxicon, 55, 754-61. https://doi.org/10.1016/j.toxicon.2009.11.008
  5. Chiang CT, Way TD, Lin JK (2007). Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21(WAF1/CIP1) expression with rapamycin. Mol Cancer Ther, 6, 2127-38. https://doi.org/10.1158/1535-7163.MCT-07-0107
  6. Gao LW, Zhang J, Yang WH et al (2011). Glaucocalyxin A induces apoptosis in human leukemia HL-60 cells through mitochondria-mediated death pathway. Toxicol In Vitro, 25, 51-63. https://doi.org/10.1016/j.tiv.2010.09.006
  7. Hendrickx N, Volanti C, Moens U, et al (2003). Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. J Biol Chem, 278, 52231-9. https://doi.org/10.1074/jbc.M307591200
  8. Hong SS, Lee SA, Han XH, et al (2008). ent-Kaurane diterpenoids from Isodon japonicus. J Nat Prod, 71, 1055-8. https://doi.org/10.1021/np0705965
  9. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  10. Kiaris H, Schally AV, Sun B, et al (1999). Inhibition of growth of human malignant glioblastoma in nude mice by antagonists of bombesin/gastrin-releasing peptide. Oncogene, 18, 7168-73. https://doi.org/10.1038/sj.onc.1203213
  11. Kim BW, Koppula S, Hong SS, et al (2013). Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-kappaB and p38 MAPK signaling pathways. PLoS One, 8, e55792. https://doi.org/10.1371/journal.pone.0055792
  12. Kim BW, Koppula S, Kim IS, et al (2011). Anti-neuroinflammatory activity of Kamebakaurin from Isodon japonicus via inhibition of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathway in activated microglial cells. J Pharmacol Sci, 116, 296-308. https://doi.org/10.1254/jphs.10324FP
  13. Lawen A (2003). Apoptosis-an introduction. Bioessays, 25, 888-96. https://doi.org/10.1002/bies.10329
  14. Lee HT, Kim SK, Cho MR I, et al (2013). Effects of the activated mitogen-activated protein kinase pathway via the c-ros receptor tyrosine kinase on the T47D breast cancer cell line following alcohol exposure. Oncol Rep, 29, 868-74.
  15. Liu WH, Chang LS (2011). Fas/FasL-dependent and -independent activation of caspase-8 in doxorubicin-treated human breast cancer MCF-7 cells: ADAM10 down-regulation activates Fas/FasL signaling pathway. Int J Biochem Cell Biol, 43, 1708-19. https://doi.org/10.1016/j.biocel.2011.08.004
  16. Lu B, Hu M, Liu K, Peng J (2010). Cytotoxicity of berberine on human cervical carcinoma HeLa cells through mitochondria, death receptor and MAPK pathways, and in-silico drug-target prediction. Toxicol In Vitro, 24, 1482-90. https://doi.org/10.1016/j.tiv.2010.07.017
  17. Minko T, Batrakova EV, Li S, et al (2005). Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells. J Control Release, 105, 269-78. https://doi.org/10.1016/j.jconrel.2005.03.019
  18. Miyoshi Y, Murase K, SaitoK Oh M (2010). Prediction of hormone sensitivity for breast cancers. Breast Cancer, 17, 86-91. https://doi.org/10.1007/s12282-009-0177-x
  19. Nakano IH, Kornblum I (2006). Brain tumor stem cells. Pediatr Res, 59, R54-8. https://doi.org/10.1203/01.pdr.0000203568.63482.f9
  20. Steeg PS (2006). Tumor metastasis: mechanistic insights and clinical challenges. Nat Med, 12, 895-904. https://doi.org/10.1038/nm1469
  21. Strasser A, JostS Nagata PJ (2009). The many roles of FAS receptor signaling in the immune system. Immunity, 30, 180-92. https://doi.org/10.1016/j.immuni.2009.01.001
  22. Sun HD, Huang SX, Han QB (2006). Diterpenoids from Isodon species and their biological activities. Nat Prod Rep, 23, 673-98. https://doi.org/10.1039/b604174d
  23. Sun Y, Zou M, Hu C, et al (2013). Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway. Food Chem Toxicol, 51, 53-60. https://doi.org/10.1016/j.fct.2012.09.012
  24. Veronesi U, Orecchia R, Luini A, et al (2010). Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Res Treat, 124, 141-51. https://doi.org/10.1007/s10549-010-1115-5
  25. Wagner EF, Nebreda AR (2009). Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer, 9, 537-49. https://doi.org/10.1038/nrc2694
  26. Weston CR, Davis RJ (2002). The JNK signal transduction pathway. Curr Opin Genet Dev, 12, 14-21. https://doi.org/10.1016/S0959-437X(01)00258-1
  27. Yang WH, Zhang Z, Sima YH, et al (2013). Glaucocalyxin A and B-induced cell death is related to GSH perturbation in human leukemia HL-60 cells. Anticancer Agents Med Chem, 13, 1280-90. https://doi.org/10.2174/18715206113139990200
  28. Zhang Z, Miao L, Lv C, et al (2013). Wentilactone B induces G2/M phase arrest and apoptosis via the Ras/Raf/MAPK signaling pathway in human hepatoma SMMC-7721 cells. Cell Death Dis, 4, e657. https://doi.org/10.1038/cddis.2013.182
  29. Zhang ZB, Jiang XG, Liang ZQ, Gu ZL (2012). Arsenic trioxide inhibits the growth of human glioma stem cells through activating the JNK pathway. Mol Cell Toxicol, 187-93.

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