Antitumor activity of a 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone copper complex and the related mechanism.

Abstract

In the present study, 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone (PPAH) was prepared and its antitumor activity was evaluated. The inhibition of proliferation of PPAH against the HepG2 and HCT-116 cell lines was less effective, yet in the presence of copper ions, the mixture demonstrated excellent antitumor activity (IC50 at 2.75±0.30µM for the HepG2 cell line, and 1.90±0.20µM for the HCT-116 cell line, respectively) and the new active species was confirmed to be a PPAH copper complex with a 1:1 ratio by spectral analysis. The excellent antitumor activity of the copper complex prompted us to investigate the underlying mechanism. RT-PCR was performed to detect the changes in the expression of apoptotic genes induced by PPAH and its copper complex. However, no changes were observed when the cells were treated by the agents for 24 or 48h, indicating that ROS were unlikely involved. Cell cycle analysis showed that both PPAH and its copper complex led to Sphase arrest of the cells. The sDNA relaxation assay revealed that the PPAH-copper complex displayed dual topoisomerase inhibition for typeI and II. The data suggest that the inhibition of proliferation exhibited by the PPAH copper complex may stem from its dual topoisomerase inhibition, which is rarely observed for a metal complex.