Solanum lyratum extracts induce extrinsic and intrinsic pathways of apoptosis in WEHI-3 murine leukemia cells and inhibit allograft tumor

Jai Sing Yang, Chia Chun Wu, Chao Lin Kuo, Yu Hsuan Lan, Chin Chung Yeh, Chien Chih Yu, Jin Cherng Lien, Yuan Man Hsu, Wei Wen Kuo, W. Gibson Wood, Minoru Tsuzuki, Jing Gung Chung

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Abstract

We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced by Solanum lyratum extracts (SLE) or diosgenin in WEHI-3 murine leukemia cells in vitro and antitumor activity in vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and induced G 0 G 1 phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (m). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. The in vivo study demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-induced G 0 G 1 phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activity in vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.

Original languageEnglish (US)
Article number254960
JournalEvidence-based Complementary and Alternative Medicine
Volume2012
DOIs
StatePublished - 2012

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