Divaricoside Exerts Antitumor Effects, in Part, by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells

Computational and Structural Biotechnology Journal
Jing-Ru WengTzong-Ming Shieh

Abstract

Cardiac glycosides (CGs), prescribed to treat congestive heart failure and arrhythmias, exert potent antitumor activity. In this study, divaricoside (DIV), a CG isolated from Strophanthus divaricatus was examined for its antitumor potency in oral squamous cell carcinoma (OSCC) cells. Cell growth was inhibited by DIV in a dose- and time-dependent manner in SCC2095 and OECM-1 OSCC cells using MTT assays. DIV induced S and G2/M phase arrest accompanied by downregulation of phosphorylated CDC25C, CDC25C, and CDC2 in SCC2095 cells. In addition, DIV induced apoptosis by activating caspase-3 and downregulating the expression of Mcl-1. Furthermore, overexpression of Mcl-1 partially reversed DIV-induced death in SCC2095 cells. Additionally, western blot and transmission electron microscopy analyses also indicated that DIV induced autophagy in SCC2095 cells. However, the combination of autophagy inhibitor did not affect DIV-mediated apoptosis in SCC2095 cells. Together, these findings suggest that translational potential of DIV to be developed as a therapeutic agent for OSCC treatment.

Citations

Nov 20, 2019·Medicinal Research Reviews·Tuhina KhanGiuseppe Campiani
Oct 30, 2020·International Journal of Molecular Sciences·Jing-Ru WengChia-Hsien Feng

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Methods Mentioned

BETA
nuclear magnetic resonance
Transfection
flow cytometry
transmission electron microscopy
Electron microscopy

Software Mentioned

ModFitLT

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