OAMDP, a novel podophyllotoxin derivative, induces apoptosis, cell cycle arrest and autophagy in hepatoma HepG2 cells.

4-(1,3,4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin (OAMDP), a novel podophyllotoxin derivative, has demonstrated potent anti-tumor activity with significant cytotoxic effect. Here, we report the anti-proliferative effect of OAMDP, for which OAMDP could suppress the proliferation of HepG2 cells (human hepatoma cell line) in a dose- and time-dependent manner. After treating with OAMDP, cell apoptosis was confirmed by Annexin V-FITC/PI double staining assay. Furthermore, flow cytometry analysis revealed the loss of mitochondrial membrane potential and the increase of intracellular reactive oxygen species in HepG2 cells. OAMDP increased apoptotic cell population with induction of Bax, cytochrome c (cyt-c), caspase-9, caspase-3, PARP1 and the reduction of Bcl-2 and p-Akt protein expressions. The MAPK family, JNK, ERK, p38, p-JNK, p-ERK, p-p38, were also regulated by OAMDP in HepG2 cells. Moreover, cell cycle analysis showed that OAMDP induced S or G2/M phase arrest through modulation of cycle regulatory proteins. In addition, MDC staining and LC3 protein expression indicated that autophagy was induced by OAMDP in HepG2 cells. To sum up, our results suggested that OAMDP, with the ability to induce autophagy, causing cell cycle arrest and apoptosis, has potential to become a novel anti-tumor agent.