Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway

摘要: We aimed to investigate the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers neem tree (Azadirachta indica) on human breast cancer cells. The molecular mechanisms involved apoptotic activity exerted by nimbolide were studied estrogen dependent (MCF-7) independent (MDA-MB-231) cell lines. growth inhibitory effect was assessed MTT assay. Apoptosis induction treatment determined JC-1 mitochondrial membrane potential staining, cytochrome c release, caspase activation, cleavage PARP AO/EtBr dual staining. modulation proteins (intrinsic pathway: Bax, bad, Bcl-2, Bcl-xL, Mcl-1, XIAP-1 caspase-3, 9; extrinsic TRAIL, FasL, FADDR Caspase-8) western blot real time PCR analysis. Treatment with resulted dose time-dependent inhibition MCF-7 MDA-MB-231 occurrence apoptosis these cells indicated both intrinsic signaling molecules expression further confirmed These events associated with: increased levels proapoptotic Bad, Fas-L, FADDR, reduced anti-apoptotic Mcl-1 XIAP-1. Nimbolide induces pro-caspase-8, pro-caspase-3 PARP. above data suggest that pathways. With evidence it is suggested exhibit anticancer through its apoptosis-inducing property. Thus, raises new hope for use therapy.