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

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Abstract

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.

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Funding

This work was supported by Key Research Project of University, Department of Education of Henan Province (Grant No. 20A350019), Henan Provincial University Science and Technology Innovation Team, Department of Education of Henan Province (Grant No. 19IRTSTHN001) and Key Project of Science and Technology, Department of Science and Technology of Henan Province (Grant No. 202102310127).

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Authors and Affiliations

  1. State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Guiqin Hou, Ang Jia, Li Yang, Yu Zhao, Yi Hu, Wen Zhao, Hong-Min Liu & Zhaoming Lu

  2. Center of Advanced Analysis & Gene Sequencing, Zhengzhou University, Zhengzhou, 450001, China

    Wuduo Zhao

  3. Collaborative Innovation Center of Cancer Chemoprevention, Henan Province, Zhengzhou, 450001, China

    Zhaoming Lu

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  1. Guiqin Hou
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Hou, G., Jia, A., Yang, L. et al. OP16 induces deadly autophagy and apoptosis of cells by inhibiting Akt in esophageal squamous cell carcinoma. Mol Cell Biochem 472, 219–230 (2020). https://doi.org/10.1007/s11010-020-03800-z

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