白藜蘆醇誘導子宮頸癌細胞凋亡

Resveratrol Induced Apoptosis in Human Cervix Epithelial Carcinoma Cells

詹文雄(Wen-Hsiung Chan)

《臺灣農業化學與食品科學》 43卷5期 (2005/10) Pp. 341-348

https://doi.org/10.6578/TJACFS.2005.043

摘要

白藜蘆醇是植物多酚類化合物的一員，富含於葡萄和其他的膳食植物中，具有抑制腫瘤生成和惡化的功能。白藜蘆醇具有廣泛的藥理效應，包括預防心臟異常、防止脂蛋白氧化以及抑制血小板凝集。而白藜蘆醇的抗癌特性被歸因於其具有抗氧化和抑制環氧化酶1和2活化的特性。此外，此抗癌能力可能也與其可造成細胞週期停止和誘導細胞凋亡的能力有關。無論如何，白藜蘆醇誘導細胞凋亡的訊息傳遞機制尚不清楚。本研究發現白藜蘆醇可誘導細胞凋亡相關生化變化的進行，包括DNA斷裂、c-Jun N端蛋白質激酶(c-Jun N terminal kinase, JNK)的活化、粒線體內細胞色素C的游離釋放以及蛋白質分解酶caspase-3的活化。利用c-Jun N端蛋白質激酶的專一性抑制劑SP600l25可有效降低白華蘆醇所導致的c-Jun N端蛋白質激醃活化，同時也抑制了蛋白酵caspase-3的活化和細胞凋亡的進行，可見c-Jun N端蛋白質激醃的活化是白藜蘆醇誘導蛋白質分解酶caspase-3活化所必須的。此外，本研究亦發現白藜蘆醇所誘導的HeLa細胞凋亡機制會增加Bax蛋白的表現，但是與Fas所參與的細胞凋亡途徑無關。綜合以上結果，本研究證實白藜蘆醇導致HeLa細胞凋亡的機制是經由起動c-Jun N端蛋白質激酶的活化、Bax蛋白的表現以及細胞色素C的游離釋放，接著導致蛋白酶caspase-3的活化以及後續凋亡變化的發生，而Fas接受器並沒有參與此凋亡過程。

關鍵字

白藜蘆醇 ； 細胞凋亡 ； 細胞色素C ； 蛋白質分解酶caspase-3

並列摘要

Resveratrol, a member of the family of phytoalexins found in grapes and other dietary plants, inhibits tumor initiation and progression. Resveratrol exhibits a wide range of pharmacological effects, including the prevention of heart disorders, blocking of lipoprotein oxidation, and inhibition of platelet aggregation. The anti-tumor properties of resveratrol are attributed to its antioxidant activity and inhibition of cyclooxygenase 1 and 2 activation. In addition, this anti-tumor activity may be due to its ability to cause cell cycle arrest and induce apoptosis. However, the signal transduction mechanisms of resveratrol-induced apoptosis are not well understood. This study showed that resveratrol could induce apoptotic biochemical changes, including DNA fragmentation, JNK activation, mitochondrial release of cytochrome c, and caspase-3 activation in HeLa cells. In addition, this study found that SP600l25, a JNK-specific inhibitor, reduced resveratrol-induced JNK activation as well as caspase-3 activation and cell apoptosis, indicating that JNK activity is required for resveratrol-induced caspase activation and cell apoptosis. Moreover, this report also showed that the Bax expression increased in resveratrol-treated HeLa cells but they were not involved in Fas apoptotic signal pathway. Collectively, these results demonstrate that apoptotic signal pathway of resveratrol-treated HeLa cells is JNK activation, Bax expression, cytochrome c release, caspase activation and subsequent apoptotic biochemical changes, and show that Fas receptor is not involved in this process.

並列關鍵字

Resveratrol ； Apoptosis ； Cytochrome c ； Caspase-3