OP16 induces deadly autophagy and apoptosis of cells by inhibiting Akt in esophageal squamous cell carcinoma

Background: OP16, a derivative of the novel ent-kaurene diterpenoid compound separated from Rabdosia rubescens, has been confirmed for its efficacy and safety in the treatment of esophageal squamous cell carcinoma (ESCC) in our previous study. However, the precise mechanisms of tumor lethality mediated by OP16 have not yet been fully characterized.

Aims: To investigate the effects and molecular mechanism of OP16 on Autophagy and Apoptosis of ESCC cells.

Methods: Effects and mechanism of OP16 on Autophagy of ESCC cells were first detected by Western blot, immunofluorescence, mRFP-GFP-LC3 adenovirus Infection and transmission electron microscope. Next, function of Autophagy and Apoptosis induced by OP16 on cell death was investigated by flow cytometry and CCK-8 assay. Finally, molecular mechanism of OP16 affecting Autophagy and Apoptosis of ESCC cells was explored by Western blot.

Results: We demonstrated that OP16 could induce Autophagy by promoting the formation of autophagosome and autolysosome, and promote autophagic cell death in ESCC. Furthermore, we also found that OP16 could promote cell Apoptosis by activating mitochondria Apoptosis pathway in ESCC. Finally, we demonstrated that OP16 affecting Autophagy and mitochondria Apoptosis pathway was mediated by phosphorylation of Akt.

Conclusion: Our data show that OP16 could promote cell death through affecting Autophagy and mitochondria Apoptosis pathway mediated by Akt in ESCC, which enriches the theoretical mechanism of anti-tumor effects of OP16 and provides a basis for treatment of OP16 on ESCC.