Cucurbitacin-I exhibits anticancer activity by inducing apoptosis in SKOV3 human ovarian cancer cells

Abstract

Background

Cucurbitacin-I is a natural cell-permeable triterpenoid compound isolated from Cucurbitaceae and Cruciferae. The pharmacological activity of cucurbitacin-I in human ovarian cancer has been rarely reported.

Objective

The purpose of this study was to investigate the anticancer effect of cucurbitacin-I in SKOV3 human ovarian cancer cells.

Methods

SKOV3 cells were treated with different concentrations of cucurbitacin-I. Cell viability was then measured by CCK-8 assay. Apoptosis, mitochondrial membrane potential, and reactive oxygen species changed by cucurbitacin-I treatment in SKOV3 cells were measured using a Muse Cell Analyzer. Expression levels of various proteins were detected by Western blot analysis.

Results

A decrease in cell viability was observed in SKOV3 cells with cucurbitacin-I treatment. In addition, in SKOV3 cells treated with cucurbitacin-I, a significant increase in apoptosis, increased activity of various caspases, destruction of mitochondrial membrane potential, and generation of reactive oxygen species were observed compared to the control group. At the protein level, an increase in cleaved caspases and Bax/Bcl-2 ratio was induced by cucurbitacin-I treatment in SKOV3 cells. Finally, the levels of phosphorylated human epidermal growth factor receptor 2 (HER2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 1 (AKT) and forkhead box O3a (FOXO3a) proteins were significantly reduced in cucurbitacin-I treated SKOV3 cells.

Conclusion

Our data demonstrate that cucurbitacin-I induces SKOV-3 cell death by inducing apoptosis via inhibition of HER2 phosphorylation and its downstream signaling molecules including PI3K, AKT and FOXO3a. This suggests a potential therapeutic role of cucurbitacin-I against ovarian cancer.