Nimbolide, a neem limonoid abrogates canonical NF-魏B and Wnt signaling to induce caspase-dependent apoptosis in human hepatocarcinoma (HepG2) cells

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• 作者：Krishnamurthy Kavitha^a ; Ramamurthi Vidya Priyadarsini^a ; Prabukumar Anitha^a ; Krishnan Ramalingam^b ; Ramasamy Sakthivel^b ; Gempuraj Purushothaman^b ; Abhishek Kumar Singh^a ; Devarajan Karunagaran^b ; Siddavaram Nagini^a ; ^{s_nagini@yahoo.com} ; ^{snlabau@gmail.com}
• 关键词：HepG2 ; Intrinsic apoptosis ; NF-魏B ; Nimbolide ; Wnt/尾-catenin
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 April, 2012
• 卷：681
• 期：1-3
• 页码：6-14
• 文件大小：1632 K

摘要

Nuclear factor kappa B (NF-魏B), an oncogenic signaling factor plays a critical role in the development and progression of various cancers. The objective of this study was to investigate the effect of nimbolide, a neem derived tetranortriterpenoid on NF-魏B signaling and its downstream events 鈥?Wnt/尾-catenin activation and apoptosis evasion in human hepatocarcinoma (HepG2) cells by evaluating NF-魏B family members (NF-魏B-p50, p65, I魏B-伪, p-I魏B-伪, and IKK尾), members of Wnt signaling (GSK-3尾 and 尾-catenin), and intrinsic apoptosis (Bcl-2, Bax, cytochrome c, Smac/DIABLO, caspase-3, and caspase-9). Our results demonstrate that nimbolide concurrently abrogates canonical NF-魏B and Wnt signaling and induces intrinsic apoptosis in HepG2 cells. These data suggest that phytochemicals such as nimbolide that can target multiple steps along the NF-魏B signaling circuit are promising candidates for future phytochemical-based mechanistic pathway targeted anticancer regimens.