辣椒素經由TRPV1傳遞與AIF轉錄引發MCF-7 細胞死亡

Capsaicin induced MCF-7 cell death via TRPV1 expression and AIF translocation

周志中(Chu-Chung Chou)

指導教授 ： 周明仁

中山醫學大學/醫學院/醫學研究所/博士(2009年)

https://doi.org/10.6834/CSMU.2009.00013

摘要

辣椒素（Capsaicin）是存在於辣椒屬中多種不同紅辣椒植物的主要刺激性成分，屬於vanilloid成員之一。研究指出辣椒素對許多癌細胞株（例如肝癌、子宮頸癌及食道癌等）均具有生物活性，能抑制細胞生長。在不表現凋亡蛋白酶3（caspase-3）的人類乳房腫瘤細胞株MCF-7中，辣椒素亦會抑制細胞生長，且隨著辣椒素濃度的增加，其抑制作用愈明顯，並可觀察到細胞凋亡的發生。本研究進一步探討辣椒素在MCF-7細胞中引發細胞凋亡的分子機制，並分析辣椒素與凋亡蛋白酶非依賴型路徑（caspase-independent pathway）的關係。MCF-7細胞經過24小時辣椒素處理後會發生劑量依存型（dose-dependent）細胞凋亡。在辣椒素處理5分鐘後，細胞內活性氧分子（reactive oxygen species; ROS）即有微量下降趨勢；處理2小時後，細胞內鈣離子濃度也有上升現象。MCF-7細胞的粒線體膜電位也會因辣椒素的處理而下降。辣椒素處理24小時後，凋亡誘導因子（apoptosis-inducing factor；AIF）會從粒線體中被釋放並進入細胞核內，這意味著辣椒素可能經由凋亡蛋白酶非依賴型路徑引發MCF-7細胞凋亡。此外，辣椒素可能直接進入細胞或穿透細胞膜誘發細胞死亡，而TRPV1蛋白會增加細胞對辣椒素的敏感性。因此，辣椒素具有成為乳癌治療藥物的潛力。

關鍵字

辣椒素 ； 乳癌 ； 凋亡蛋白酶MCF-7 ； 凋亡誘導因子

並列摘要

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a major pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloids. It has been shown to exert biological activities in many cancer cell lines. It was found that capsaicin induces dose-dependent growth inhibition of MCF-7 cells, which do not express caspase-3. In this study, we investigated the molecular mechanism of capsaicin-induced apoptosis in MCF-7 cells. Treatment with capsaicin for 24 hours resulted in a dose-dependent apoptosis in MCF-7 cells. After addition of capsaicin, levels of reactive oxygen species (ROS) reduced slightly in the earlier time of treatment. Interestingly, an elevation of intracellular calcium ion (Ca2+) concentration was also detected in MCF-7 cells. It is worth noting that apoptosis-inducing factor (AIF) translocated into the cytosol and nucleus from mitochondria, suggesting that capsaicin may induce cellular apoptosis through caspase-independent pathway in MCF-7 cells. Furthermore, capsaicin may directly enter the cell or penetrate cell membrane to induce cell death and the expression of TRPV1 could increase the sensitivity of capsaicin for cells. Hence, capsaicin may be a potent drug in breast cancer therapy.

並列關鍵字

Capsaicin ； Breast cancer ； Caspase ； MCF-7 ； Apoptosis- inducing factor.

參考文獻

1. Byers T, Nestle M, McTiernan A, Doyle C, Currie-Williams A, Gansler T, et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2006 Sep-Oct;56(5):254-81.

2. World_Health_Organization. WHO Fact sheet No. 297: Cancer. In: World Health Organization; 2006.

3. Paschka AG, Butler R, Young CY. Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate. Cancer Lett. 1998 Aug 14;130(1-2):1-7.

4. Smets LA. Programmed cell death (apoptosis) and response to anti-cancer drugs. Anticancer Drugs. 1994 Feb;5(1):3-9.

5. Cordell GA, Araujo OE. Capsaicin: identification, nomenclature, and pharmacotherapy. Ann Pharmacother. 1993 Mar;27(3):330-6.