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Curcumin Inhibits Human Non-small Cell Lung Cancer A549 Cell Proliferation Through Regulation of Bcl-2/Bax and Cytochrome C

  • Li, Yue (Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University) ;
  • Zhang, Shuai (Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University) ;
  • Geng, Jian-Xiong (Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University) ;
  • Hu, Xiao-Yang (Staff Room of Prescription, Heilongjiang University of Chinese Medicine)
  • Published : 2013.08.30

Abstract

We intended to study the mechanism of the inhibitory action of curcumin on human non-small cell lung cancer A549 cell. The cell growth was determined by CCK-8 assay, and the results indicated that curcumin inhibited the cell proliferation in a concentration dependent manner. And to further confirm the relative anti-cancer mechanism of curcumin, RT-PCR was carried out to analysis the expression of relative apoptotic proteins Bax, Bcl-2. We found that curcumin could up-regulate the expression of Bax but down-regulate the expression of Bcl-2 in A549 cells. In addition, curcumin affect the mitochondrial apoptosis pathway. These results suggested that curcumin inhibited cancer cell growth through the regulation of Bcl-2/Bax and affect the mitochondrial apoptosis pathway.

Keywords

References

  1. Aggarwal S, Ichikawa H, Takada Y, et al (2006). Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol, 69, 195-206.
  2. Bansal SS, Goel M, Aqil F, Vadhanam MV, Gupta RC (2011). Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila), 4, 1158-71. https://doi.org/10.1158/1940-6207.CAPR-10-0006
  3. Howells LM, Mitra A, Manson MM (2007). Comparison of oxaliplatin- and curcumin-mediated antiproliferative effects in colorectal cell lines. Int J Cancer, 121, 175-83. https://doi.org/10.1002/ijc.22645
  4. Jaiswal AS, Marlow BP, Gupta N, Narayan S (2002). Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene, 21, 8414-27. https://doi.org/10.1038/sj.onc.1205947
  5. Na HS, Cha MH, Oh DR, et al (2011). Protective mechanism of curcumin against Vibrio vulnificus infection. FEMS Immunol Med Microbiol, 63, 355-62. https://doi.org/10.1111/j.1574-695X.2011.00855.x
  6. National Collaborating Centre for Cancer (UK) (2011). The Diagnosis and Treatment of Lung Cancer (Update). Cardiff (UK): National Collaborating Centre for Cancer (UK).
  7. Notarbartolo M, Poma P, Perri D, et al (2005). Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett, 224, 53-65. https://doi.org/10.1016/j.canlet.2004.10.051
  8. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  9. Pettersson F, Dalgleish AG, Bissonnette RP, Colston KW (2002). Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax. Br J Cancer, 87, 555-61. https://doi.org/10.1038/sj.bjc.6600496
  10. Sato T, Hanada M, Bodrug S, et al (1994). Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system. Proc Natl Acad Sci U S A, 91, 9238-42. https://doi.org/10.1073/pnas.91.20.9238
  11. Schaffer M, Schaffer PM, Zidan J, Bar Sela G (2011). Curcuma as a functional food in the control of cancer and inflammation. Curr Opin Clin Nutr Metab Care, 14, 588-97. https://doi.org/10.1097/MCO.0b013e32834bfe94
  12. Song JX, Sze SC, Ng TB, et al (2012). Anti-Parkinsonian drug discovery from herbal medicines: what have we got from neurotoxic models? J Ethnopharmacol, 139, 698-711. https://doi.org/10.1016/j.jep.2011.12.030
  13. Speciale A, Chirafisi J, Saija A, Cimino F (2011). Nutritional antioxidants and adaptive cell responses: an update. Curr Mol Med, 11, 770-89. https://doi.org/10.2174/156652411798062395
  14. Wang YJ, Niu XP, Yang L, Han Z, Ma YJ (2013). Effects of celecoxib on cycle kinetics of gastric cancer cells and protein expression of cytochrome C and caspase-9. Asian Pac J Cancer Prev, 14, 2343-7. https://doi.org/10.7314/APJCP.2013.14.4.2343
  15. Xu Y, Zhang JJ, Han J, et al (2012). Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha1-antitrypsin in lung cancer. Mol Oncol, 6, 405-17. https://doi.org/10.1016/j.molonc.2012.03.005
  16. Yang CL, Liu YY, Ma YG, et al (2012). Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS One, 7, e37960. https://doi.org/10.1371/journal.pone.0037960
  17. Youle RJ, Strasser A (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol, 9, 47-59. https://doi.org/10.1038/nrm2308

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