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

• Main Authors: Syam, Suvitha, Bustamam, Ahmad, Abdullah, Rasedee, Sukari, Mohd Aspollah, Mohd Hashim, Najihah, Ghaderian, Mostafa, Rahmani, Mawardi, Mohan, Syam, Abdelwahab, Siddig Ibrahim, Mohd Ali, Hapipah
• Format: Article
• Language: English
• Published: Elsevier 2014
• Online Access: http://psasir.upm.edu.my/id/eprint/36671/1/%CE%B2.pdf; http://psasir.upm.edu.my/id/eprint/36671/

β-Mangostin (βM) was isolated from Cratoxylum arborescens to investigate its anti-cancer effect in MCF-7 cells. βM 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, βM had showed p53-dependent G2/M cell cycle arrest by down regulation of cdc2 and PCNA. Together, the results demonstrated that the βM 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.