4β-Hydroxywithanolide E對人類肺癌細胞凋亡機制研究

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標題:	4β-Hydroxywithanolide E對人類肺癌細胞凋亡機制研究 The apoptoic mechanism of 4β-hydroxywithanolide E in human A549 cells
作者:	鐘珮蓉 Pei-jung Chung
貢獻者:	吳淑靜嘉南藥理科技大學：生物科技研究所
關鍵字:	秘魯酸漿細胞凋亡 Physalis peruviana L. apoptosis Bax Bcl-2 Ca Caspase-3 PARP XIAP
日期:	2007
上傳時間:	2008-12-03 11:15:55 (UTC+8)
摘要:	秘魯酸漿Physalis peruviana L. (PP) 是一種民間廣泛使用生藥， 4 β-hydroxywithanolide E (HWE)化合物自秘魯酸漿Physalis peruviana的莖及葉部位分離之純化物。A549人類肺癌細胞分別以HWE與5-FU處理，進行抗肺癌活性先篩選出強效之抗癌藥物，再進行細胞凋亡機制研究。結果發現A549細胞中HWE呈現較高的抗癌活性。細胞以HWE作用經24小時處理後，會減弱S期的細胞表現量。另外，細胞凋亡中Sub-G1百分比，當HWE 濃度由1 μg/ml提高到20 μg/ml時，Sub-G1百分比會提高自4.77±0.39%到69.33±2.98% 呈現劑量效應。結果發現Bcl-2及XIAP蛋白質會隨劑量及時間效應表現呈遞減趨勢。HWE也會藉由提高Bax蛋白質表現、Caspase-3活性及PARP分裂而造成細胞凋亡。綜合上述結果推論HWE驅動A549細胞凋亡可能是經由調節Bcl-2家族(Bax及Bcl-2)蛋白質及IAP家族(XIAP及c-IAP1)蛋白質所導致。 Physalis peruviana L. (PP) is a herb widely used in folk medicine. 4 β-hydroxywithanolide E (HWE) compound isolated from the P. peruviana. The study further confirmed that HWE inhibited cell proliferation and induced cell apoptosis in the human A549 cells. In general, HWE displayed a higher anti-cancer activity than WS. After 24 h of treatment, HWE decreased in the S phase of cell in a dose response manner. In addition, 1~20 μg/ml HWE showed a dose-dependent accumulation of the Sub-G1 peak by increasing from 4.77±0.39% to 69.33±2.98%. The results showed a marked down-regulation of Bcl-2 and XIAP proteins in a dose- and a time-dependent manner. HWE also inhibited cell proliferation through up-regulation of Bax protein, activation of Caspase-3 and PARP cleavage. Taken together, the results conclude that HWE triggers apoptosis in A549 cells could be through the modulation of Bcl-2 family (Bax and Bcl-2) proteins and IAP family (XIAP and c-IAP1) proteins.
關聯:	校內一年後公開，校外永不公開
顯示於類別:	[生物科技系(所)] 博碩士論文

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