Apoptosis induced by podophyllotoxin derivative OAMDP in HeLa cells

A novel podophyllotoxin derivative, 4β-(1, 3, 4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin(OAMDP), showed the antiproliferative effect, for which OAMDP could suppress the proliferation of HeLa cells in a dose-and time-dependent manner. Furthermore, its molecular mechanism in HeLa cells was investigated. In HeLa cells treated by OAMDP, topical morphological changes of apoptotic body formation were observed by Hoechst 33258 staining. Cell apoptosis was also confirmed by Annexin Ⅴ-FITC/PI double staining assay. Rhodamine 123 label testing revealed that the mitochondrial membrane potential(ΔΨm)of cells was decreased. OAMDP increased apoptotic cell population by induction of bax and reduction of Bcl-2 expression. Moreover, cell cycle analysis showed that OAMDP induced S phase arrest in HeLa cells. Our results indicated that OAMDP, with the ability to cause cell cycle S arrest and apoptosis, has the potential to become a novel antitumor agent.