Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Ursolic Acid Promotes Apoptosis of SGC-7901 Gastric Cancer Cells through ROCK/PTEN Mediated Mitochondrial Translocation of Cofilin-1

  • Li, Rui (Department of Clinical Laboratories, the Fifth People's Hospital of Shenyang and Tumor Hospital of Shenyang) ;
  • Wang, Xia (Department of Clinical Laboratories, the Fifth People's Hospital of Shenyang and Tumor Hospital of Shenyang) ;
  • Zhang, Xiao-Hong (Department of Clinical Laboratories, the Fifth People's Hospital of Shenyang and Tumor Hospital of Shenyang) ;
  • Chen, Hong-Hai (Department of Clinical Laboratories, the Fifth People's Hospital of Shenyang and Tumor Hospital of Shenyang) ;
  • Liu, Yan-Dong (Department of Clinical Laboratories, the Fifth People's Hospital of Shenyang and Tumor Hospital of Shenyang)
  • Published : 2014.12.18
Download PDF
⟨ Previous Next ⟩

Abstract

Ursolic acid, extracted from the traditional Chinese medicine bearberry, can induce apoptosis of gastric cancer cells. However, its pro-apoptotic mechanism still needs further investigation. More and more evidence demonstrates that mitochondrial translocation of cofilin-1 appears necessary for the regulation of apoptosis. Here, we report that ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis. These findings imply that induction of apoptosis by ursolic acid stems primarily from the activation of ROCK1 and PTEN, resulting in the translocation of cofilin-1 from cytoplasm to mitochondria, release of cytochrome c, activation of caspase-3 and caspase-9, and finally inducing apoptosis of gastric cancer SGC-7901 cells.

Keywords

References

  1. Anderson D, Liu JJ, Nilsson A, et al (2003). Ursolic acid inhibits proliferation and stimulates apoptosis in HT29 cells following activation of alkaline sphingomyelinase. Anticancer Res, 23, 3317-22.
  2. Bamburg JR, Bernstein BW (2010). Roles of ADF/cofilin in actin polymerization and beyond. F1000 Biol Rep, 2, 62.
  3. Chen G, Shen ZL, Wang L, et al (2013). Hsa-miR-181a-5p expression and effects on cell proliferation in gastric cancer. Asian Pac J Cancer Prev, 14, 3871-5. https://doi.org/10.7314/APJCP.2013.14.6.3871
  4. Chen H, Bernstein BW, Bamburg JR (2000). Regulating actinfilament dynamics in vivo. Trends Biochem Sci, 25, 19-23. https://doi.org/10.1016/S0968-0004(99)01511-X
  5. Chua BT, Volbracht C, Tan KO, et al (2003). Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat Cell Biol, 5, 1083-9. https://doi.org/10.1038/ncb1070
  6. Green DR, Kroemer G (2004). The pathophysiology of mitochondrial cell death. Science, 305, 626-9. https://doi.org/10.1126/science.1099320
  7. Jang I, Jeon BT, Jeong EA, et al (2012). Pak1/LIMK1/Cofilin pathway contributes to tumour migration and invasion in human non-small cell lung carcinomas and cell lines. Korean J Physiol Pharmacol, 16, 159-65. https://doi.org/10.4196/kjpp.2012.16.3.159
  8. Klamt F, Zdanov S, Levine RL, et al (2009). Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin. Nat Cell Biol, 11, 1241-46. https://doi.org/10.1038/ncb1968
  9. Li GB, Cheng Q, Liu L, et al (2013). Mitochondrial translocation of cofilin is required for allylisothiocyanate-mediated cell death via ROCK1/PTEN/PI3K signaling pathway. Cell Commun Signal, 11, 50. https://doi.org/10.1186/1478-811X-11-50
  10. Li P, Nijhawan D, Budihardjo I, et al (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91, 479-89. https://doi.org/10.1016/S0092-8674(00)80434-1
  11. Li Z, Dong X, Wang Z, et al (2005). Regulation of PTEN by Rho small GTPases. Nat Cell Biol, 7, 399-404. https://doi.org/10.1038/ncb1236
  12. Ma CM, Cai SQ, Cui JR, et al (2005). The cytotoxic activity of ursolic acid derivatives. Eur J Med Chem, 40, 582-9. https://doi.org/10.1016/j.ejmech.2005.01.001
  13. Pathak AK, Bhutani M, Nair AS, et al (2007). Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol Cancer Res, 5, 943-55. https://doi.org/10.1158/1541-7786.MCR-06-0348
  14. Polachini GM, Sobral LM, Mercante AM, et al (2012). Proteomic approaches identify members of cofilin pathway involved in oral tumorigenesis. PLoS One, 7, 50517. https://doi.org/10.1371/journal.pone.0050517
  15. Popow-Wozniak A, Mazur AJ, Mannherz HG, et al (2012). Cofilin overexpression affects actin cytoskeleton organization and migration of human colon adenocarcinoma cells. Histochem Cell Biol, 138, 725-36. https://doi.org/10.1007/s00418-012-0988-2
  16. Rehklau K, Gurniak CB, Conrad M, et al (2012). ADF/cofilin proteins translocate to mitochondria during apoptosis but are not generally required for cell death signaling. Cell Death Differ, 19, 958-67. https://doi.org/10.1038/cdd.2011.180
  17. Sugimura T, Kawachi T (1975). Abnormal differentiation of human gastric epithelium. Dev Growth Differ, 17, 299-300. https://doi.org/10.1111/j.1440-169X.1975.00299.x
  18. Wang CH, Zhou GL, Vedantam S, et al (2008). Mitochondrial shuttling of CAP1 promotes actin- and cofilin dependent apoptosis. J Cell Sci, 121, 2913-20. https://doi.org/10.1242/jcs.023911
  19. Wang X (2001). The expanding role of mitochondria in apoptosis. Genes Dev, 15, 2922-33.
  20. Wang X, Zhang F, Yang L, et al (2011). Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo. J Biomed Biotechnol, 2011, 419343.
  21. Xu JL, Wang ZW, Hu LM, et al (2012). Genetic variants in the PI3K/PTEN/AKT/ mTOR pathway predict platinum-based chemotherapy response of advanced non-small cell lung cancers in a Chinese population. Asian Pac J Cancer Prev, 13, 2157-62. https://doi.org/10.7314/APJCP.2012.13.5.2157
  22. Zhou J, Wang Y, Fei J, et al (2012). Expression of cofilin 1 is positively correlated with the differentiation of human epithelial ovarian cancer. Oncol Lett, 4, 1187-90.

Cited by

  1. Ursolic acid derivative FZU-03,010 inhibits STAT3 and induces cell cycle arrest and apoptosis in renal and breast cancer cells vol.49, pp.4, 2017, https://doi.org/10.1093/abbs/gmx012
  2. Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer vol.12, pp.4, 2016, https://doi.org/10.3892/ol.2016.5015