PMID: 11911251Mar 26, 2002Paper

Augmentation of apoptosis responses in p53-deficient L1210 cells by compounds directed at blocking NFkappaB activation

Anticancer Research
A H Cory, J G Cory

Abstract

A mouse leukemia L1210 cell line (Y8) selected for resistance to deoxyadenosine was found to be deficient in the expression of p53 mRNA and protein while maintaining the expression of WAF1/p21 mRNA and protein even under basal conditions. The Y8 cells were shown to be more sensitive to apoptosis induced by a variety of agents when compared to the parental wild-type (WT) L1210 cells. Roscovitine, an inhibitor of cdk 2 and cdk5, was one of the agents that caused increased apoptosis in the Y8 cells through a pathway that ultimately involved the activation of caspase-3 activity. In these studies, the effects of leflunomide and parthenolide (drugs reported to alter the activation of NFkappaB in a variety of cell types) were studied for their cell cycle and apoptotic effects in WT and Y8 cells as single agents and in combination with roscovitine. Leflunomide at IC50 concentrations had little effect on the cell cycle distribution of either the WT or Y8 cells while at higher concentrations caused a G0/G1 block in Y8 cells. Parthenolide, at IC50 concentrations, caused a G0/G1 cell cycle block in the WT and Y8 cells but at higher concentrations caused a G2/M block in the Y8 cells. The combinations of leflunomide and roscovitine or parthe...Continue Reading

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