Phenanthroimidazole derivatives act as potent inducer of autophagy by activating DNA damage pathway

A series of imidazo[4,5f][1,10] phenanthroline derivatives (1-6) have been synthesized in this study, and their inhibitory activity was evaluated by MTT assay. Results showed that all of these compounds demonstrate a promising inhibitory activity against a panel of human cancer cell lines. The 6, the most effective compound with IC50 of approximately 2.3 +/- 0.1 mu M, was against the growth and could induce autophagy of HepG2 cells. This condition was confirmed by abundant autophagic vacuoles appearing in cells and evident ultrastructural changes observed under transmission electron microscopy. The autophage induced by 6 has also been demonstrated by up-regulating LC3-II and Beclin1. The apoptosis and G2/M phase cell cycle arrest through DSB damage have also been confirmed after the HepG2 cells were treated by 6. These multiple effects, especially induction apoptosis and autophagy, indicate the potential of 6 for development as a novel anticancer drug.