p21 Waf-1 (Cip-1) enhances apoptosis induced by XXXX and @entity1311 in @entity259 cells.

@entity522 @entity3544 @entity1311 @entity47491 @entity259
Our previous studies demonstrated that @entity47491 (a farnesyltransferase inhibitor) enhanced the antineoplastic activity and induction of apoptosis when combined with @entity1311 against @entity259 cells. We found that @entity47491 induces endogenous expression of @entity3544 Waf-1 in @entity259 cells. @entity47491 increased the activity of the p21promoter, the level of @entity3544 mRNA, and the amount of @entity3544 protein. We hypothesized that @entity3544 had a proapoptotic effect in cells treated with @entity47491 , or @entity1311 , or both agents. By measuring viability and @entity522 activity, we found that stably transfected KAT-4 cells with @entity3544 cDNA under the control of a metallothionein promoter were more sensitive to @entity47491 alone, @entity1311 alone, and @entity47491 plus @entity1311 when @entity3544 was induced. The increased sensitivity of the cells with induced @entity3544 was associated with an increase in @entity522 activity (i.e. apoptosis). We also found that cells with both @entity3544 alleles deleted were less sensitive to @entity47491 plus @entity1311 than its wild-type parent cells. Expression of @entity3544 per se did not induce apoptosis but enhanced the cytotoxic effects of @entity47491 and @entity1311 . These findings suggested that @entity3544 might be required to maintain cell sensitivity to the cytotoxic effects of @entity47491 and @entity1311 .
