Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteins

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Chenyao Ruan1, Chen Wang1,2, Jiawen Gu1

  • 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Plos One
|November 7, 2024
PubMed
Abstract

Insights

Isoscopoletin exhibits anti-tumor effects against hepatocellular carcinoma (HCC) by inhibiting glycolysis. It targets key proteins like GPD2, GPI, Hsp90α, and PGK2, thus blocking cancer cell energy supply.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Isoscopoletin, a metabolite of scoparone, shows potential anti-tumor properties.
  • Hepatocellular carcinoma (HCC) is a major global health concern with limited treatment options.

Purpose of the Study:

  • To investigate the anti-cancer mechanism of isoscopoletin against HCC.
  • To elucidate the role of glycolysis regulation in isoscopoletin's anti-HCC effects.

Main Methods:

  • Transcriptomics to identify affected pathways.
  • Network pharmacology and molecular docking to predict targets.
  • Microscale thermophoresis (MST) to validate protein binding.
  • In vitro assays for glucose consumption, lactate production, and protein expression (RT-qPCR, ELISA).

Main Results:

  • Transcriptomics revealed enrichment in glycolysis and metabolic pathways.
  • GPD2, GPI, HSP90AA1, and PGK2 identified as core targets.
  • Isoscopoletin demonstrated strong binding affinity to these targets.
  • In vitro studies confirmed inhibition of glucose uptake and lactate production, with altered protein levels.

Conclusions:

  • Isoscopoletin exerts anti-tumor effects on HCC by targeting GPD2, GPI, Hsp90α, and PGK2.
  • This regulation inhibits the glycolysis pathway, crucial for cancer cell energy metabolism.
  • Isoscopoletin represents a potential therapeutic agent for HCC by disrupting tumor cell energy supply.

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