Involvement of ERK, Bcl-2 family and caspase 3 in recombinant human activin A-induced apoptosis in A549.

Abstract

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). CONCLUSION 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.

DOI: 10.1016/j.tox.2009.01.023

Cite this paper

@article{Wang2009InvolvementOE, title={Involvement of ERK, Bcl-2 family and caspase 3 in recombinant human activin A-induced apoptosis in A549.}, author={Baiding Wang and Yuling Feng and Xingbo Song and Qingqing Liu and Yunye Ning and Xuemei Ou and Jie Yang and Xiaohong Zhang and Fu-qiang Wen}, journal={Toxicology}, year={2009}, volume={258 2-3}, pages={176-83} }