Dioscin inhibits SCC15 cell proliferation via the RASSF1A/MST2/YAP axis

Mol Med Rep. 2021 Jun;23(6):414. doi: 10.3892/mmr.2021.12053. Epub 2021 Mar 31.

Abstract

Dioscin, an extract from traditional Chinese herbal plants, displays various biological and pharmacological effects on tumors, including inhibition of cell proliferation and induction of DNA damage. However, the effects of dioscin on oral squamous cell carcinoma (OSCC) cells are not completely understood. The present study aimed to evaluate the impact of dioscin on OSCC cell proliferation. Cell Counting Kit‑8 and 5‑ethynyl‑2'‑deoxyuridine incorporation assays were performed to assess cell proliferation. Flow cytometry was conducted to detect alterations in the cell cycle and cell apoptosis. Western blotting and coimmunoprecipitation were performed to determine protein expression levels. In SCC15 cells, dioscin treatment significantly induced cell cycle arrest, increased apoptosis and inhibited proliferation compared with the control group. Mechanistically, the tumor suppressor protein Ras association domain‑containing protein 1A (RASSF1A) was activated and oncoprotein yes‑associated protein (YAP) was phosphorylated by dioscin. Furthermore, YAP overexpression and knockdown reduced and enhanced the inhibitory effects of dioscin on SCC15 cells, respectively. In summary, the results demonstrated that, compared with the control group, dioscin upregulated RASSF1A expression in OSCC cells, which resulted in YAP phosphorylation, thus weakening its transcriptional coactivation function, enhancing cell cycle arrest and apoptosis, and inhibiting cell proliferation. The present study indicated that dioscin may serve as a therapeutic agent for OSCC.

Keywords: dioscin; yes‑associated protein; Ras association domain‑containing protein 1A; proliferation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Diosgenin / analogs & derivatives*
  • Diosgenin / pharmacology
  • Humans
  • Mouth Neoplasms / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Serine-Threonine Kinase 3
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • RASSF1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • dioscin
  • Protein Serine-Threonine Kinases
  • STK3 protein, human
  • Serine-Threonine Kinase 3
  • Diosgenin

Grants and funding

The present study was supported by the Shandong Provincial Natural Science Foundation (grant no. ZR2018MH018), China Postdoctoral Science Foundation (grant no. 2017M610432) and Young Scholars Program of Shandong University (grant no. 2015WLJH53).