Effect of trichostatin A on cell growth and expression of cell cycle- and apoptosis-related molecules in human gastric and oral carcinoma cell lines

The effect of trichostatin A (TSA), histone deacetylase inhibitor, on cell growth and the mechanism of growth modulation was examined in 8 gastric and 3 oral carcinoma cell lines which included 9-cis-retinoic acid resistant ( MKN-7 and Ho-I-N-I) and IFN-beta resistant cell lines (MKN-7, -28 and -45). TSA inhibited growth in all cell lines examined. Apoptotic cell death was confirmed by apoptotic ladder formation and induction of a cleaved form (85 kDa) of poly (ADP-ribose) polymerase (PARP) induction. TSA enhanced the pr otein expression of p21(WAF1), CREB-binding protein, cyclinE, cyclin A, Bak and Fax, while it reduced the expression of E2F-1, E2F-4, HDAC1, p53 and h yperphosphorylated form of ph. Furthermore, TSA induced morphological chang es, such as elongation of cytoplasm and cell-to-cell detachment, in gastric and oral carcinoma cell lines. These results suggest that TSA may inhibit cell growth and induce apoptosis of gastric and oral carcinoma cells throug h modulation of the expression of cell cycle regulators and apoptosis-regul ating proteins. Int. J, Cancer 88:992-997, 2000, (C) 2000 Wiley-Liss, Inc.