Role of p53 in cdk Inhibitor VMY-1-103-Induced Apoptosis in Prostate Cancer.

摘要

Cyclin-dependent kinase inhibitor VMY-1-103 induces a G2/M cell cycle arrest and apoptosis in prostate cancer cell lines. Cancer cell lines, including prostate cancer, show a differential sensitivity to VMY-1-103 that correlates with p53 status. In addition, VMY-1-103 sensitivity increases in cancer cell lines as compared with normal cell lines, regardless of p53 status. Knockdown experiments in LNCaP cells show a reduced sensitivity to VMY-1-103 by resulting in a decreased cell death and this result can be rescued by the addition of wild-type p53. Transient transfections of wild-type p53 into p53- null PC-3 cells resulted in increased cell death upon VMY treatment. Furthermore, PRIMA-1 pre-treatment restored p53 activity in p53-mutant DU145 cells and sensitized them to VMY-mediated cell death. As compared with other solid tumors, only a small percentage of prostate cancer cases contain p53 mutations. Therapeutically, this is important as a majority of prostate cancer patients could benefit from VMY.