INDUCTION OF APOPTOSIS BY ACYCLIC RETINOID IN THE HUMAN HEPATOMA-DERIVED CELL-LINE, HUH-7

HuH-7 cells, a human hepatoma-derived cell line, underwent apoptosis i n response to all-trans 3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexad ecapentaenoic acid, or acyclic retinoid. The retinoid-induced apoptosi s was verified by a characteristic step-wise fragmentation of genomic DNA and chromatin condensation. The induction of apoptosis was detecte d as early as 8 hrs after the addition of the retinoid and was concent ration dependent(0.1 similar to 10 mu M). Neither the natural retinoid all-trans retinoic acid nor 9-cis retinoic acid induced apoptosis. Th ese data strongly indicate that the antitumor activity of the acyclic retinoid may be partly explained by the induction of apoptosis in tumo r cells. (C) 1995 Academic Press, Inc.