Barbigerone, a natural isoflavone, induces apoptosis in murine lung-cancer cells via the mitochondrial apoptotic pathway.
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.
Li
Zheng-Guang
ZG
Department of Gynecology and Obstetrics, Second West China Hospital, Chengdu 610041, China.
Zhao
Ying-Lan
YL
Wu
Xiaohua
X
Ye
Hao-Yu
HY
Peng
Aihua
A
Cao
Zhi-Xing
ZX
Mao
Yong-Qiu
YQ
Zheng
Yu-Zhu
YZ
Jiang
Pei-Du
PD
Zhao
Xia
X
Chen
Li-Juan
LJ
Wei
Yu-Quan
YQ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D007529:Isoflavones; D019253:Proto-Oncogene Proteins c-bcl-2; C543999:barbigerone; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053453:Caspase 9