Sarkar Arnab, Bhattacharjee Shamee, Mandal Deba Prasad
Department of Zoology, West Bengal State University, Berunanpukuria, Malikapur, Kolkata, West Bengal, India E-mail :
Asian Pac J Cancer Prev. 2015;16(15):6753-9. doi: 10.7314/apjcp.2015.16.15.6753.
Loss of function of the p53 gene is implicated in defective apoptotic responses of tumors to chemotherapy. Although the pro-apoptotic roles of eugenol and capsaicin have been amply reported, their dependence on p53 for apoptosis induction in gastric cancer cells is not well elucidated. The aim of the study was to elucidate the role of p53 in the induction of apoptosis by eugenol and capsaicin in a human gastric cancer cell line, AGS.
AGS cells were incubated with or without various concentrations of capsaicin and eugenol for 12 hrs, in the presence and absence of p53 siRNA. Cell cycling, annexin V and expression of apoptosis related proteins Bax, Bcl-2 ratio, p21, cyt c-caspase-9 association, caspase-3 and caspase-8 were studied.
In the presence of p53, capsaicin was a more potent pro-apoptotic agent than eugenol. However, silencing of p53 significantly abrogated apoptosis induced by capsaicin but not that by eugenol. Western blot analysis of pro-apoptotic markers revealed that as opposed to capsaicin, eugenol could induce caspase-8 and caspase-3 even in the absence of p53.
Unlike capsaicin, eugenol could induce apoptosis both in presence and absence of functional p53. Agents which can induce apoptosis irrespective of the cellular p53 status have immense scope for development as potential anticancer agents.
p53基因功能丧失与肿瘤对化疗的凋亡反应缺陷有关。尽管丁香酚和辣椒素的促凋亡作用已有大量报道，但其在胃癌细胞中诱导凋亡对p53的依赖性尚未得到充分阐明。本研究的目的是阐明p53在人胃癌细胞系AGS中丁香酚和辣椒素诱导凋亡过程中的作用。
在有无p53小干扰RNA的情况下，将AGS细胞与不同浓度的辣椒素和丁香酚孵育12小时。研究细胞周期、膜联蛋白V以及凋亡相关蛋白Bax、Bcl-2比值、p21、细胞色素c-半胱天冬酶-9结合、半胱天冬酶-3和半胱天冬酶-8的表达。
在有p53的情况下，辣椒素比丁香酚是更有效的促凋亡剂。然而，p53沉默显著消除了辣椒素诱导的凋亡，但未消除丁香酚诱导的凋亡。促凋亡标志物的蛋白质印迹分析显示，与辣椒素不同，即使在没有p53的情况下，丁香酚也能诱导半胱天冬酶-8和半胱天冬酶-3。
与辣椒素不同，丁香酚在有和没有功能性p53的情况下均可诱导凋亡。无论细胞p53状态如何都能诱导凋亡的药物作为潜在抗癌药物具有巨大的开发前景。
