Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Parthenolide-Induced Apoptosis, Autophagy and Suppression of Proliferation in HepG2 Cells

  • Sun, Jing (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Zhang, Chan (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Bao, Yong-Li (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Wu, Yin (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Chen, Zhong-Liang (Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education) ;
  • Yu, Chun-Lei (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Huang, Yan-Xin (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Sun, Ying (Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education) ;
  • Zheng, Li-Hua (National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University) ;
  • Wang, Xue (China-Japan Union Hospital of Jilin University) ;
  • Li, Yu-Xin (Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education)
  • Published : 2014.06.30
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Abstract

Purpose: To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells. Materials and Methods: Cell viability was assessed by MTT assay and cell apoptosis through DAPI, TUNEL staining and Western blotting. Monodansylcadaverin(MDC) and AO staining were used to detect cell autophagy. Cell proliferation was assessed by Ki67 immunofluorescence staining. Results: Parthenolide induced growth inhibition in HepG2 cells. DAPI and TUNEL staining showed that parthenolide could increase the number of apoptotic nuclei, while reducing the expression of the anti-apoptotic protein Bcl-2 and elevating the expression of related proteins, like p53, Bax, cleaved caspase9 and cleaved caspase3. Parthenolide could induce autophagy in HepG2 cells and inhibited the expression of proliferation-related gene, Ki-67. Conclusions: Parthenolide can exert anti-cancer effects by inducing cell apoptosis, activating autophagy and inhibiting cell proliferation.

Keywords

References

  1. Avila MA, Berasain C, Sangro B, et al (2006). New therapies for hepatocellular carcinoma. Oncogene, 25, 3866-84. https://doi.org/10.1038/sj.onc.1209550
  2. Biederbick A, Kern HF, Elsasser HP (1995). Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles. Eur J Cell Biol, 6, 3-14.
  3. Cui J, Gong Z, Shen HM (2013). The role of autophagy in liver cancer: molecular mechanisms and potential therapeutic targets. Biochim Biophys Acta, 1836, 15-26.
  4. DU P, Cao H, Wu HR (2013). Blocking Bcl-2 Leads to autophagy activation and cell death of the HEPG2 liver cancer cell line. Asian Pac J Cancer Prev, 14, 5849-54. https://doi.org/10.7314/APJCP.2013.14.10.5849
  5. Gerdes J, Lemke H, Baisch H, et al (1984). Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol, 133, 1710-5.
  6. Gomaa AI, Khan SA, Toledano MB, et al (2008). Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol, 14, 4300-8. https://doi.org/10.3748/wjg.14.4300
  7. Green DR, Evan GI (2002). A matter of life and death. Cancer Cell, 1, 19-30. https://doi.org/10.1016/S1535-6108(02)00024-7
  8. Kaseb AO, Abaza YM, Roses RE (2013). Multidisciplinary management of hepatocellular carcinoma. Recent Results Cancer Res, 190, 247-59. https://doi.org/10.1007/978-3-642-16037-0_16
  9. Knight DW (1995). Feverfew, chemistry and biological activity. Nat Prod Rep, 12, 271-6. https://doi.org/10.1039/np9951200271
  10. Kondo Y, Kanzawa T, Sawaya R, et al (2005). The role of autophagy in cancer development and response to therapy. Nat Rev Cancer, 5, 726-34. https://doi.org/10.1038/nrc1692
  11. Kwok BH, Koh B, Ndubuisi MI, et al (2001). The antiinflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol, 8, 759-66. https://doi.org/10.1016/S1074-5521(01)00049-7
  12. Leong S, McKay MJ, Christopherson RI, et al (2012). Biomarkers of breast cancer apoptosis induced by chemotherapy and TRAIL. J Proteome Res, 11, 1240-50. https://doi.org/10.1021/pr200935y
  13. Levine B, Kroemer G (2008). Autophagy in the pathogenesis of disease. Cell, 132, 27-42. https://doi.org/10.1016/j.cell.2007.12.018
  14. Lizuka N, Miyamoto K, Okita K, et al (2000). Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett, 148, 19-25. https://doi.org/10.1016/S0304-3835(99)00264-5
  15. Lockshin RA, Zakeri Z (2004). Caspase-independent cell death. Oncogene, 23, 2766. https://doi.org/10.1038/sj.onc.1207514
  16. Mains RE, May V (1988). The role of a low pH intracellular compartment in the processing, storage, and secretion of ACTH and endorphin. J Biol Chem, 263, 7887-94.
  17. Mathema VB, Koh YS, Thakuri BC, et al (2012). Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation, 35, 560-5. https://doi.org/10.1007/s10753-011-9346-0
  18. Mizushima N (2004). Methods for monitoring autophagy. Int J Biochem Cell B, 36, 2491-502. https://doi.org/10.1016/j.biocel.2004.02.005
  19. Newman DJ (2008). Natural products as leads to potential drugs: an old process or the new hope for drug discovery. J Med Chem, 51, 2589-99. https://doi.org/10.1021/jm0704090
  20. Obiol-Pardo C, Granadino-Roldan JM, Rubio-Martinez J (2008). Protein-protein recognition as a first step towards the inhibition of XIAP and Survivin anti-apoptotic proteins. J Mol Recognit, 21, 190-204. https://doi.org/10.1002/jmr.887
  21. Overholtzer M, Mailleux AA, Mouneimne G, et al (2007). A nonapop-totic cell death process, entosis, that occurs by cell-in-cell invasion. Cell, 131, 966-79. https://doi.org/10.1016/j.cell.2007.10.040
  22. Paglin S, Hollister T, Delohery T, et al (2001). A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res, 61, 439-44.
  23. Parada-Turska J, Paduch R, Majdan M, et al (2007). Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells. Pharmacol Rep, 59, 233-7.
  24. Riedl SJ, Shi Y (2004). Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol, 5, 897-907. https://doi.org/10.1038/nrm1496
  25. Rocha AB, Lopes RM, Schwartsmann G (2001). Natural products in anticancer therapy. Curr Opin Pharmacol, 1, 364-9. https://doi.org/10.1016/S1471-4892(01)00063-7
  26. Shu KX, Li B, Wu LX (2007). The p53 network: p53 and its downstream genes. Colloids Surf B, 55, 10-8. https://doi.org/10.1016/j.colsurfb.2006.11.003
  27. Signore M, Ricci-Vitiani L, De Maria R (2012). Targeting apoptosis pathways in cancer stem cells. Cancer Lett, 332, 374-82.
  28. Sobota R, Szwed M, Kasza A, et al (2000). Parthenolide inhibits activation of signal transducers and activators of transcription (STATs) induced by cytokines of the IL-6 family. Biochem Biophys Res Commun, 267, 329-33. https://doi.org/10.1006/bbrc.1999.1948
  29. Wang X (2001). The expanding role of mitochondria in apoptosis. Genes, 15, 2922-33.
  30. Zhang S, Ong CN, Shen HM (2004). Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Lett, 208, 143-53. https://doi.org/10.1016/j.canlet.2003.11.028
  31. Zhang S, Ong CN, Shen HM (2004). Involvement of proapoptotic bcl-2 family members in parthenolide-induced mitochondrial dysfunction and apoptosis. Cancer Lett, 211, 175-88. https://doi.org/10.1016/j.canlet.2004.03.033
  32. Zhang Y, Chen AY, Li M, Chen C, et al (2008). Ginkgo biloba extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. J Surg Res, 148, 17-23. https://doi.org/10.1016/j.jss.2008.02.036
  33. Zunino SJ, Ducore JM, Storms DH (2007). Parthenolide induces significant apoptosis and production of reactive oxygen species in high-risk pre-B leukemia cells. Cancer Lett, 254, 119-27. https://doi.org/10.1016/j.canlet.2007.03.002

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