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

Journal of Functional Foods

Rasedee Abdullah¹  Mostafa Ghaderian¹  Ahmad Bustamam²  Mawardi Rahmani³  Mohamed Aspollah Sukari³  Siddig Ibrahim Abdelwahab⁴  Hapipah Mohd Ali⁵  Syam Mohan⁶  Suvitha Syam⁷  Najihah Mohd Hashim⁷ 

[1] Corresponding authors. Address: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia (S. Syam). Tel.: [phone];Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;fax: [phone].;Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia;Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;Department of Veterinary Pathology and Microbiology, Faculty of Veterinary, University Putra Malaysia, Serdang, Selangor, Malaysia;UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia;

关键词: Cratoxylum arborescens;    β-Mangostin;    Apoptosis;    p53;    NF-kB;    Bax/Bcl-2;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown