Inhibiting the Src/STAT3 signaling pathway contributes to the anti-melanoma mechanisms of dioscin

Yu Xi Liu, Bo Wen Xu, Ying Jie Chen, Xiuqiong FU, Pei Li Zhu, Jing Xuan Bai, Ji Yao Chou, Cheng Le Yin, Jun Kui Li, Ya Ping Wang, Jia Ying Wu, Ying Wu, Kam Kwan Chan, Chun Liang, Zhiling YU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Late stage melanoma is associated with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3) is currently a target for melanoma treatment as it is constitutively activated with high frequency in melanoma. Dioscin is a natural steroid saponin that is present in several medical herbs. A previous study demonstrated that dioscin inhibits STAT3 signaling in a cerebral ischemia-reperfusion injury rat model. Furthermore, dioscin has been reported to exert anti-melanoma effects in B16 melanoma cells and a B16 allograft mouse model. The present study investigated whether inhibition of STAT3 signaling is involved in the anti-melanoma effects of dioscin. The results of the present study demonstrated that dioscin significantly decreased viability, induced apoptosis and suppressed migration of human A375 melanoma cells and murine B16F10 melanoma cells. Furthermore, dioscin inhibited the phosphorylation of STAT3 and Src (an upstream kinase of STAT3), and downregulated mRNA levels of STAT3-targeted genes, including B-cell lymphoma-2, cyclin D1 and matrix metalloproteinase-2. In addition, overexpression of STAT3 decreased the anti-proliferative effects of dioscin. Overall, the results of the present study indicate that inhibiting the Src/STAT3 signaling pathway contributes to the anti-melanoma molecular mechanisms of dioscin. These results provide further pharmacological groundwork for developing dioscin as a novel anti-melanoma agent.

Original languageEnglish
Pages (from-to)2508-2514
Number of pages7
JournalOncology Letters
Volume19
Issue number3
DOIs
Publication statusPublished - 2020

Scopus Subject Areas

  • Oncology
  • Cancer Research

User-Defined Keywords

  • Dioscin
  • Mechanism
  • Melanoma
  • Src
  • STAT3

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