尾-Mangostin induces p53-dependent G2/M cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway and NfkB suppression in MCF-7 cells

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• 作者：Suvitha Syam ; Ahmad Bustamam ; Rasedee Abdullah ; Mohamed Aspollah Sukari ; Najihah Mohd Hashim ; Mostafa Ghaderian ; Mawardi Rahmani ; Syam Mohan ; Siddig Ibrahim Abdelwahab ; Hapipah Mohd Ali
• 关键词：尾M ; 尾-mangostin ; MMP ; mitochondrial membrane potential ; NF-kB ; nuclear factor-kappa B ; TNF-伪 ; tumour necrosis factor alpha ; ROS ; reactive oxygen species ; DCFH-DA ; 2&prime ; 7&prime ; -dichlorofluorescein diacetate ; HCS ; high content screening ; PARP ; poly ADP ribose polymerase ; GADD ; growth arrest DNA damage ; XIAP ; X-linked inhibitor of apoptosis protein ; PMSF ; phenylmethanesulfonylfluoride
• 刊名：Journal of Functional Foods
• 出版年：January, 2014
• 年：2014
• 卷：6
• 期：Complete
• 页码：290-304
• 全文大小：3627 K

文摘

尾-Mangostin (尾M) was isolated from Cratoxylum arborescens to investigate its anti-cancer effect in MCF-7 cells. 尾M induced apoptosis by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of caspase-9 and -7 and consequently cleaved PARP leading to apoptotic was observed upon treatment. Reduction of both bid and caspase 8 and the up regulation of Fas showed the involvement of the extrinsic pathway. Significantly up regulated GADD45A and HRK genes were observed upon treatment, with concomitant inhibition of NF-kB to nucleus. The protein array had demonstrated the expression of HSP 70, HSP 60, XIAP, Survivin, p53 and Bax. Moreover, 尾M had showed p53-dependent G2/M cell cycle arrest by down regulation of cdc2 and PCNA. Together, the results demonstrated that the 尾M induced anti-proliferative effect, leading to G2/M phase cell cycle arrest and apoptosis through both the extrinsic and mitochondrial pathways with the involvement of the multiple pro and anti-apoptosis and NF-kB signalling pathways.