Transcriptional regulation of the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1), by the chelator, Dp44mT

摘要

Background: The cyclin-dependent kinase inhibitor, p21, is well known for its role in cell cycle arrest. Novel anticancer agents that deplete iron pools demonstrate marked anti-tumor activity and are also active in regulating p21 expression. These agents induce p21 mRNA levels independently of the tumor suppressor, p53, and differentially regulate p21 protein expression depending on the cell-type. Several chelators, including an analogue of the potent anti-tumor agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), have entered clinical trials, and thus, their molecular mechanism of action is crucial to assess. Hence, this investigation examined how several iron chelators transcriptionally regulate p21.