Kim Young Min, Hwang Jin-Taek, Kwak Dong Wook, Lee Yun Kyung, Park Ock Jin
Department of Food and Nutrition, Hannam University, Daejeon 306-791, Korea.
Ann N Y Acad Sci. 2007 Jan;1095:496-503. doi: 10.1196/annals.1397.053.
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.
单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）在ATP消耗的代谢状态下被激活，如缺氧、热休克、氧化应激和运动。作为一种高度保守的异源三聚体激酶，充当维持能量稳态的主要代谢开关，AMPK已被证明是哺乳动物细胞周期的内在调节因子。此外，AMPK级联反应已成为癌症控制中的一条重要途径。在本文中，我们研究了辣椒素对结肠癌细胞中与AMPK激活相关的细胞凋亡的影响。在经辣椒素处理的HT-29结肠癌细胞中，核小体的存在揭示了辣椒素诱导的细胞凋亡。同时，在经辣椒素处理的结肠癌细胞中检测到AMPK的激活以及无活性形式的乙酰辅酶A羧化酶（ACC）表达的增加。我们表明，辣椒素和AMPK激活剂5'-氨基咪唑-4-甲酰胺-1-β-D-核糖核苷（AICAR）都具有激活AMPK的能力以及诱导细胞凋亡的特性。辣椒素处理HT-29结肠癌细胞后AMPK激活与细胞凋亡增加之间的关联证据，以及AICAR和辣椒素联合处理后激活的AMPK与升高的细胞凋亡之间相关性的进一步发现，支持AMPK作为细胞凋亡的重要组成部分以及癌症控制的一个可能靶点。
