Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathway.
Flavokawain B (FKB) possesses strong anti-neoplastic activity against many cancer cells. Here we assessed its antitumor activity and molecular mechanisms in lung cancer H460 cells in vitro. FKB significantly inhibited cell proliferation and caused arrest of the cell cycle G2-M of H460 cells in a dose-dependent manner. FKB also inducted apoptosis, which was associated with cytochrome c release, caspase-7 and caspase-9 activation and Bcl-xL/Bax dys-regulation. FKB significantly down-regulated survivin and XIAP, and the inhibitory effect induced by FKB was greatly attenuated by through over-expression of survivin or Bax(-/-) MEFs. Furthermore, FKB activated the mitogen-activated protein kinases and the JNK inhibitor SP600125 significantly decreased the growth-inhibitory and apoptotic effects of FKB. Together, these results suggest the anti-lung cancer potential of flavokawain B for the prevention and treatment of lung cancer.
Chengdu Institute of Biology, Chinese Academy of Sciences, No 9 Section 4, Renmin Nan Road, Chengdu, 610041 Sichuan, People's Republic of China. anjxia@163.com
JunXia
J
An
YaRong
Y
Gao
Jing
J
Wang
QiYu
Q
Zhu
YuLing
Y
Ma
Jian
J
Wu
Jian
J
Sun
YaXiong
Y
Tang
D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494826:BAX protein, human; C107489:BIRC5 protein, human; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051028:bcl-2-Associated X Protein; C452039:flavokawain B; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases