Trichostatin A induces apoptosis of p815 mastocytoma cells in histone acetylation- and mitochondria-dependent fashion.
Although inhibition of histone deacetylase has been demonstrated to induce apoptosis of various cancer cells, there is no report on its effect on mast cell demise to date. Here we studied whether a histone deacetylase inhibitor Trichostatin A (TSA) produces apoptosis in p815 mastocytoma cells. TSA prominently increased the amount of acetylated histones, H3, H4, H2A and H2B, in p815 mastocytoma cells. TSA reduced the viability of p815 mastocytoma cells, and many apoptotic manifestations such as generation of DNA fragmentation, activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and increase of DNA hypoploidy proved that the reduction of viability resulted from apoptosis. Whereas TSA treatment increased the expression level of Bad, it decreased the level of Bcl-2, Bcl-xL, and X-linked inhibitor of apoptosis protein. The reduction of mitochondrial membrane potential, the release of cytochrome c and Smac/DIABLO to cytosol, and mitochondrial localization of Bad were also shown. Taken together, TSA induces apoptosis on p815 mastocytoma cells in histone acetylation- and mitochondria-dependent fashion. Our data therefore provide the possibility that TSA could be considered as a novel therapeutic strategy for mastocytoma from its apoptosis-inducing activity.
Yee
Su-Bog
SB
Department of Anatomy and Cell Biology (BK21 program), Dong-A University College of Medicine and Medical Science Research Center, Busan 602-714, South Korea.
Kim
Myung Soo
MS
Baek
Soo Jin
SJ
Kim
Gyoo Cheon
GC
Yoo
Ki Soo
KS
Yoo
Young Hyun
YH
Park
Bong Soo
BS
D000107:Acetylation; D000123:Acetyltransferases / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D034801:Mastocytoma / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D000123:Acetyltransferases; D051548:Histone Acetyltransferases