Apoptosis Inducing Effect of Plumbagin on Colonic Cancer Cells Depends on Expression of COX-2

被引:71
作者
Subramaniya, Bharathi Raja [1 ]
Srinivasan, Gayathri [1 ]
Sadullah, Sakeena Mohammed Sadullah [1 ]
Davis, Nimitha [1 ]
Subhadara, Lakshmi Baddi Reddi [3 ]
Halagowder, Devaraj [2 ]
Sivasitambaram, Niranjali Devaraj [1 ]
机构
[1] Univ Madras, Dept Biochem, Sch Life Sci, Chennai, Tamil Nadu, India
[2] Univ Madras, Dept Zool, Sch Life Sci, Chennai 600025, Tamil Nadu, India
[3] Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India
来源
PLOS ONE | 2011年 / 6卷 / 04期
关键词
COLORECTAL-CANCER; BETA-CATENIN; KAPPA-B; ACTIVATION; INHIBITION; MUTATIONS; ZEYLANICA; TARGET; PLANT; DNA;
D O I
10.1371/journal.pone.0018695
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Plumbagin, a quinonoid found in the plants of the Plumbaginaceae, possesses medicinal properties. In this study we investigated the anti-proliferative and apoptotic activity of plumbagin by using two human colonic cancer cell lines, HT29 and HCT15. IC50 of Plumbagin for HCT15 and HT29 cells (22.5 mu M and 62.5 mu M, respectively) were significantly different. To study the response of cancer cells during treatment strategies, cells were treated with two different concentrations, 15 mu M, 30 mu M for HCT15 and 50 mu M, 75 mu M for HT29 cells. Though activation of NF kappa B, Caspases-3, elevated levels of TNF-alpha, cytosolic Cytochrome C were seen in both HCT15 cells HT29 treated with plumbagin, aberrant apoptosis with decreased level of pEGFR, pAkt, pGsk-3 beta, PCNA and Cyclin D1was observed only in 15 mu M and 30 mu M plumbagin treated HCT15 and 75 mu M plumbagin treated HT29 cells. This suggests that plumbagin induces apoptosis in both HCT15 cells and HT29 treated, whereas, proliferation was inhibited only in 15 mu M and 30 mu M plumbagin treated HCT15 and 75 mu M plumbagin treated HT29 cells, but not in 50 mM plumbagin treated HT29 cells. Expression of COX-2 was decreased in 75 mu M plumbagin treated HT29 cells when compared to 50 mu M plumbagin treated HT29 cells, whereas HCT15 cells lack COX. Hence the observed resistance to induction of apoptosis in 50 mu M plumbagin treated HT29 cells are attributed to the expression of COX-2. In conclusion, plumbagin induces apoptosis in colonic cancer cells through TNF-alpha mediated pathway depending on expression of COX-2 expression.
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页数:11
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