Involvement of ERK, Bcl-2 family and caspase 3 in recombinant human activin A-induced apoptosis in A549.
BACKGROUND
Activins are members of the transforming growth factor-beta (TGF-beta) superfamily. Previous studies have shown that activin A may have a central role in regulating both apoptosis and proliferation. However, direct studies of recombination human activin A on human NSCLC A549 cells have not yet been reported. The purpose of this study was to investigate whether activin A could induce apoptosis in A549 cells and the possible mechanisms via which it worked.


METHODS
Cellular apoptosis induced by activin A was detected by TUNEL assay and the levels of protein expression were detected by western blot.


RESULTS
Recombination human activin A induced apoptosis in human NSCLC A549 cells in a concentrate-dependent manner. Activin A-induced A549 apoptosis was accompanied by the up-regulation of Bax, Bad and Bcl-Xs and down-regulation of Bcl-2. Moreover, activin A treatment increased the expression of its typeII receptors, activated ERK and caspase 3 in A549. These results clearly demonstrate that the induction of apoptosis by activin-A involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins and caspase 3 participate in activin A-induced apoptotic process in A549 cells. On the other hand, activin A treatment had little effect on primary human small airway epithelial cells (SAECs).


CONCLUSIONS
Recombination human activin A induced apoptosis in A549 cells, at least partially, through ERK and mitochondrial pathway. The result that activin A did not affect the normal SAEC revealed activin A might be considered as a potential anticancer agent and worthy of further studies.
Wang
Baiding
B
Division of Pulmonary Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People's Republic of China.
Feng
Yuling
Y
Song
Xingbo
X
Liu
Qingqing
Q
Ning
Yunye
Y
Ou
Xuemei
X
Yang
Jie
J
Zhang
Xiaohong
X
Wen
Fuqiang
F
D028341:Activins / Q000235:genetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; C422405:activin A; D028341:Activins; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3