Ginsenoside 20(S)-Rg3 reduces expression and promotes CDC25A proteasomal degradation in epithelial ovarian cancer.

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-κB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway.

Materials And Methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as and cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining.

Results: is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth and . Ginsenoside Rg3 can suppress the transcription of . GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (β-TrCP1), a substrate recognition subunit for SCF E3 ubiquitin ligase. ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates overexpression-induced CDC25A upregulation.

Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.