Tumor Biology

, Volume 35, Issue 3, pp 2451–2459 | Cite as

Mitochondrial translocation of cofilin-1 promotes apoptosis of gastric cancer BGC-823 cells induced by ursolic acid

  • Qingfeng Tang
  • Qing Ji
  • Yu Tang
  • Teng Chen
  • Gang Pan
  • Songjiao Hu
  • Yijie Bao
  • Wen Peng
  • Peihao Yin
Research Article


The pathogenesis of gastric cancer is characterized by excessive proliferation, abnormal differentiation, and reduced apoptosis. Ursolic acid, extracted from traditional Chinese medicine bearberry, inhibits cell growth and induces apoptosis in gastric cancer. However, the mechanism of the proapoptotic effect of ursolic acid on gastric cancer cells needs further investigation. In our present study, we found in apoptotic gastric cancer BGC-823 cells induced by ursolic acid that a translocation of cofilin-1 protein from the cytoplasm to the mitochondria promoted the release of cytochrome c from the mitochondria to the cytoplasm, thereby activating the caspase cascade and finally inducing gastric cancer cell apoptosis. These results implied that the mitochondrial translocation of cofilin-1 might play a crucial role in the promotion of apoptosis and might be a key target for future treatment of human gastric cancer.


Cofilin-1 Mitochondrial translocation Apoptosis Gastric cancer Ursolic acid 



This work was supported by the Program of Shanghai Municipal Education Commission (2012JW67), Shanghai Municipal Health Bureau (20114037), Shanghai Committee of Science and Technology, China (no. 114119b3100), Putuo District Committee of Science and Technology, Shanghai China (no. 201102), and Construct Program of the Key Discipline of State Administration of Traditional Chinese Medicine of People's Republic of China.

Conflicts of interest



  1. 1.
    Sugimura T, Kawachi T. Abnormal differentiation of human gastric epithelium. Dev Growth Differ. 1975;17:299–300.CrossRefGoogle Scholar
  2. 2.
    Aizawa K, Ueki K, Suzuki S, Yabusaki H, Kanda T, Nishimaki T, et al. Apoptosis and Bcl-2 expression in gastric carcinomas: correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol. 1999;14:85–91.PubMedGoogle Scholar
  3. 3.
    Ikeda M, Shomori K, Endo K, Makino T, Matsuura T, Ito H. Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma. Virchows Arch. 1998;432:43–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Ajani JA, Barthel JS, Bekaii-Saab T, Bentrem DJ, D'Amico TA, Das P, et al. Gastric cancer. J Natl Compr Canc Netw. 2010;8:378–409.PubMedGoogle Scholar
  5. 5.
    Ma CM, Cai SQ, Cui JR, Wang RQ, Tu PF, Hattori M, et al. The cytotoxic activity of ursolic acid derivatives. Eur J Med Chem. 2005;40:582–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Wang X, Zhang F, Yang L, Mei Y, Long H, Zhang X, et al. Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo. J Biomed Biotechnol. 2011;2011:419343.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, et al. Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol Cancer Res. 2007;5:943–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Anderson D, Liu JJ, Nilsson A, Duan RD. Ursolic acid inhibits proliferation and stimulates apoptosis in HT29 cells following activation of alkaline sphingomyelinase. Anticancer Res. 2003;23:3317–22.Google Scholar
  9. 9.
    Shishodia S, Majumdar S, Banerjee S, Aggarwal BB. Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res. 2003;63:4375–83.PubMedGoogle Scholar
  10. 10.
    Liu X, Guo DA. Application of proteomics in the mechanistic study of traditional Chinese medicine. Biochem Soc Trans. 2011;39:1348–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Cho WC. Application of proteomics in Chinese medicine research. Am J Chin Med. 2007;35:911–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Li N, Guo R, Li W, Shao J, Li S, Zhao K, et al. A proteomic investigation into a human gastric cancer cell. Carcinogenesis. 2006;27:1222–31.PubMedCrossRefGoogle Scholar
  13. 13.
    Pope BJ, Zierler-Gould KM, Kühne R, Weeds AG, Ball LJ. Solution structure of human cofilin: actin binding, pH sensitivity, and relationship to actin-depolymerizing factor. J Biol Chem. 2004;279:4840–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Gillett GT, Fox MF, Rowe PS, Casimir CM, Povey S. Mapping of human non-muscle type cofilin (CFL1) to chromosome 11q13 and muscle-type cofilin (CFL2) to chromosome 14. Ann Hum Genet. 1996;60:201–11.PubMedCrossRefGoogle Scholar
  15. 15.
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Estaquier J, Vallette F, Vayssiere JL, Mignotte B. The mitochondrial pathways of apoptosis. Adv Exp Med Biol. 2012;942:157–83.PubMedCrossRefGoogle Scholar
  17. 17.
    Zhou J, Wang Y, Fei J, Zhang W. Expression of cofilin 1 is positively correlated with the differentiation of human epithelial ovarian cancer. Oncol Lett. 2012;4:1187–90.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Jang I, Jeon BT, Jeong EA, Kim EJ, Kang D, Lee JS, et al. Pak1/LIMK1/cofilin pathway contributes to tumour migration and invasion in human non-small cell lung carcinomas and cell lines. Korean J Physiol Pharmacol. 2012;16:159–65.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Popow-Woźniak A, Mazur AJ, Mannherz HG, Malicka-Błaszkiewicz M, Nowak D. Cofilin overexpression affects actin cytoskeleton organization and migration of human colon adenocarcinoma cells. Histochem Cell Biol. 2012;138:725–36.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Chua BT, Volbracht C, Tan KO, Li R, Yu VC, Li P. Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat Cell Biol. 2003;5:1083–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Wang CH, Zhou GL, Vedantam S, Li P, Field J. Mitochondrial shuttling of CAP1 promotes actin- and cofilin dependent apoptosis. J Cell Sci. 2008;121:2913–20.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Polachini GM, Sobral LM, Mercante AM, Paes-Leme AF, Xavier FC, Henrique T, et al. Proteomic approaches identify members of cofilin pathway involved in oral tumorigenesis. PLoS One. 2012;7:e50517.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Elam WA, Kang H, De la Cruz EM. Biophysics of actin filament severing by cofilin. FEBS Lett. 2013;587:1215–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Fass J, Gehler S, Sarmiere P, Letourneau P, Bamburg JR. Regulating flopodial dynamics through actin-depolymerizing factor/cofilin. Anat Sci Int. 2004;79:173–83.PubMedCrossRefGoogle Scholar
  25. 25.
    Ghosh M, Song X, Ouneimne MG, Sidani M, Lawrence DS, Condeelis JS. Cofilin promotes actin polymerization and defines the direction of cell motility. Science. 2004;304:743–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Dawe HR, Minamide LS, Bamburg JR, Cramer LP. ADF/cofilin controls cell polarity during fibroblast migration. Curr Biol. 2003;13:252–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Pradelli LA, Bénéteau M, Ricci JE. Mitochondrial control of caspase-dependent and caspase-independent cell death. Cell Mol Life Sci. 2010;67:1589–97.PubMedCrossRefGoogle Scholar
  28. 28.
    Mayer B, Oberbauer R. Mitochondrial regulation of apoptosis. News Physiol Sci. 2003;18:89–94.PubMedGoogle Scholar
  29. 29.
    Kartsogiannis V, Ng KW. Cell lines and primary cell cultures in the study of bone cell biology. Mol Cell Endocrinol. 2004;228:79–112.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Qingfeng Tang
    • 1
  • Qing Ji
    • 1
    • 2
  • Yu Tang
    • 3
  • Teng Chen
    • 2
  • Gang Pan
    • 2
  • Songjiao Hu
    • 2
  • Yijie Bao
    • 2
  • Wen Peng
    • 3
  • Peihao Yin
    • 2
  1. 1.Department of Clinical Laboratories & Experimental Center, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  2. 2.Department of General Surgery, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  3. 3.Department of Nephrology, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina

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