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

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.