Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity

D Furuya, N Tsuji, A Yagihashi, N Watanabe - Experimental cell research, 2005 - Elsevier
D Furuya, N Tsuji, A Yagihashi, N Watanabe
Experimental cell research, 2005Elsevier
Beclin 1, identified as a Bcl-2-interacting protein, is known to enhance autophagy. However,
the effect of Beclin 1 on apoptotic signaling has remained unclear. Here, we show that
overexpression of Beclin 1 in MKN28 human gastric cancer cells augmented cis-
diamminedichloroplatinum (CDDP)-induced apoptosis. Conversely,“knockdown” of Beclin 1
by a small inhibitory RNA in MKN 1 cells attenuated this cytotoxicity. Furthermore, not only
caspase-3/7 activities, but also caspase-9 activity was increased in Beclin 1 gene …
Beclin 1, identified as a Bcl-2-interacting protein, is known to enhance autophagy. However, the effect of Beclin 1 on apoptotic signaling has remained unclear. Here, we show that overexpression of Beclin 1 in MKN28 human gastric cancer cells augmented cis-diamminedichloroplatinum (CDDP)-induced apoptosis. Conversely, “knockdown” of Beclin 1 by a small inhibitory RNA in MKN 1 cells attenuated this cytotoxicity. Furthermore, not only caspase-3/7 activities, but also caspase-9 activity was increased in Beclin 1 gene transfectants treated with CDDP, and caspase-9 inhibitor completely abolished augmentation of CDDP-induced apoptosis by Beclin 1 as did a caspase-3 inhibitor. Thus, Beclin 1 augments CDDP-induced apoptosis through enhancing caspase-9 activity and functions as a pro-apoptotic molecule.
Elsevier