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Barbigerone, a Natural Isoflavone, Induces Apoptosis in Murine Lung-Cancer Cells via the Mitochondrial Apoptotic PathwayLi Z.-G.1,* · Zhao Y.-L.1,* · Wu X.1,* · Ye H.-Y.1 · Peng A.1 · Cao Z.-X.1 · Mao Y.-Q.1 · Zheng Y.-Z.1 · Jiang P.-D.1 · Zhao X.2 · Chen L.-J.1 · Wei Y.-Q.1
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 1Department of Gynecology and Obstetrics, Second West China Hospital,2West China Medical School, Sichuan University, Chengdu 610041, China,*These authors contributed equally to this work Corresponding Author
Yu-Quan Wei and Li-Juan Chen
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital
West China Med School, Sichuan University, 1 Keyuan Road 4, Gaopeng Street
High Technological Development Zone, Chengdu 610041 (China)
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Barbigerone is a naturally occurring isoflavone with antioxidant activity. In present study, we investigated the antitumor activity of barbigerone against murine lung cancer cells LL/2 and the possible mechanism in vitro. Our results showed that barbigerone inhibited LL/2 cells proliferation in a concentration- and time-dependent manner and caused apoptotic death of LL/2 cells. Barbigerone-induced apoptosis was characterized by enhanced mitochondrial cytochrome c release, activation of caspase-3,-9, but not caspase-8. Exposure of LL/2 cells to barbigerone resulted in upregulation of Bcl-2-associated protein (Bax) and down-regulation of Bcl-2. In addition, proliferation inhibitory effect of barbigerone was associated with decreased level of phosphorylated p42/44 mitogen-activated protein kinase (p42/44 MAPK) and phosphorylated Akt. Moreover, barbigerone exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, our results indicated that barbigerone can inhibit murine lung cancer cell proliferation by inducing apoptosis via mitochondrial apoptotic pathway and by decreasing phosphorylated p42/44 MAPK and Akt. Its potential to be a candidate of anti-cancer agent is worth being further investigated.
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