Implication of p53 in growth arrest and apoptosis induced hy the syntheticretinoid CD437 in human lung cancer cells

CD437 is a novel retinoid that can induce apoptosis in a variety of tumor c ell types by an unknown mechanism. We found that CD437 up-regulated the exp ression of p21(WAF1/CIP1), Bar, and Killer/DR5 and induced G(1) arrest and rapid apoptosis in three human non-small cell lung carcinoma cell lines wit h wild-type p53 but not in five cell lines with mutant p53, suggesting a ro le for p53 in the effects of CD437. Using H460 cells in which,wild-type p53 protein was degraded by transfection of the human papillomavirus 16 E6 (HP V-16 E6) gene and H460 cells transfected with a control plasmid only, we fo und that CD437 increased p53, p21(WAF1/CIP1), Bax and Killer/DR5 in the con trol transfectants, In contrast, the constitutive p53 protein level was sup pressed, and the ability of CD437 to increase p53 and its downstream genes was compromised in E6 transfectants, In addition, CD437 induced G(1) arrest and apoptosis in the control transfectants but not in the E6-transfected c ells. These results indicate that p53 plays a role in CD137-induced growth inhibition and apoptosis in human non-small cell lung carcinoma cells.