Podophyllotoxin enfeebles human oral squamous cell carcinoma through Myeloid cell leukemia-1

Abstract

Background Podophyllotoxin (PPT), which is derived from the podophyllum plant, exhibits marked cytotoxic effects against cancer cells; however, the specific molecular mechanism behind its activity against human oral squamous cell carcinoma (OSCC) is unknown. In this study, we determined the mechanism by which PPT induces cytotoxicity in two OSCC cell lines, HSC3 and HSC4. Methods In this study, the underlying molecular mechanism effects of PPT on cytotoxicity in HSC3 and HSC4 cells were analyzed using Sub-G1 analysis, Annexin V/PI double staining, soft agar assay, Western blotting, and quantitative PCR. The change in the mitochondrial membrane potential was assessed using JC-1 assay and cytosolic and mitochondrial fraction. We also constructed an myeloid cell leukemia‑1 (Mcl-1) overexpression vector and performed transient transfection to study the role of Mcl-1 on apoptosis. Results The results showed that PPT inhibits the growth of two human OSCC cell lines and triggers apoptosis, accompanied by mitochondrial membrane depolarization. Compared with controls, PPT reduced the expression of Mcl‑1 in both cell lines through a proteasome-dependent protein degradation process. Conclusions Overall, our results suggest that the reduction of Mcl-1 protein by PPT induces apoptosis, which provides a foundation for its continued pre-clinical and clinical study in OSCC.