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Artesunate as an Anti-Cancer Agent Targets Stat-3 and Favorably Suppresses Hepatocellular Carcinoma

M Ilamathi, S Santhosh, V Sivaramakrishnan1

  • 1Department of Bioinformatics, CTOR Lab, School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur-613401, Tamilnadu, India. sivaramakrishnan@scbt.sastra.edu.

Current Topics in Medicinal Chemistry
|February 14, 2016
PubMed
Abstract

Insights

Artesunate (ATS) shows potential as a hepatocellular carcinoma (HCC) therapeutic by inhibiting signal transducer and activator of transcription 3 (STAT-3) signaling. This small molecule effectively suppresses cancer cell growth and promotes apoptosis in vitro.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • Aberrant signal transducer and activator of transcription 3 (STAT-3) signaling is implicated in hepatocellular carcinoma (HCC) development.
  • Targeting STAT-3 presents a promising therapeutic strategy for HCC suppression.

Purpose of the Study:

  • To identify a small molecule inhibitor that specifically targets STAT-3 for HCC suppression.
  • To evaluate sesquiterpene lactone (STL) candidates as potential STAT-3 inhibitors.

Main Methods:

  • Utilized a unified computational and experimental approach to analyze STL candidates.
  • Assessed Artesunate's (ATS) inhibitory effects on STAT-3 activity, dimerization, and downstream targets in vitro.
  • Investigated ATS's impact on STAT-3 DNA binding and its cytotoxicity against cancer cells.

Main Results:

  • Artesunate (ATS) identified as a potent STAT-3 inhibitor, comparable to S3I-201.
  • ATS inhibited IL-6 driven STAT-3-DNA binding and STAT-3 dimerization in vitro.
  • ATS modulated STAT-3 dependent pro-apoptotic targets and exhibited selective cytotoxicity towards HCC cells.

Conclusions:

  • The study suggests ATS has potential as a therapeutic agent against HCC.
  • ATS demonstrates efficacy through STAT-3 inhibition, promoting apoptosis and selective cancer cell cytotoxicity.
  • Combined computational and in vitro data support ATS's role in HCC therapy.

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