Related Experiment Video

Updated: Jul 5, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

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Annonaceous Acetogenins Synergistically Inhibit Hepatocellular Carcinoma with Sorafenib

Rong-Sheng Li1, Ling-Yun Li1, Xiao-Feng Zhu1

  • 1School of Pharmacy, Fudan University, Shanghai 201203, China.

Journal of Natural Products
|January 18, 2024
PubMed

Insights

Annona montana seed extracts, particularly annonacin, show synergistic effects with sorafenib for advanced hepatocellular carcinoma (HCC). This combination enhances antitumor activity and promotes apoptosis, offering a potential new therapy.

Area of Science:

  • Natural Product Chemistry
  • Pharmacology
  • Oncology

Background:

  • Sorafenib is a standard treatment for advanced hepatocellular carcinoma (HCC) but has limitations in efficacy and side effects.
  • Combination therapy is explored to improve sorafenib's effectiveness and reduce toxicity.

Purpose of the Study:

  • To investigate the synergistic antitumor activity of Annona montana seed extracts with sorafenib against advanced HCC.
  • To isolate and identify active compounds from Annona montana and evaluate their potential in combination therapy.

Main Methods:

  • Bioguided fractionation of Annona montana seed extracts.
  • Isolation and structural elucidation of seven annonaceous acetogenins, including three novel compounds.
  • In vitro and in vivo assays to evaluate synergistic cytotoxicity and antitumor activity with sorafenib.
  • Transcriptomic analysis to predict the mechanism of action of annonacin.

Main Results:

  • Seven acetogenins, including muricin P, Q, and R, were isolated and identified.
  • Annonacin and muricin P demonstrated synergistic cytotoxicity with sorafenib in vitro by reducing ATP levels and inducing apoptosis.
  • Annonacin showed synergistic antitumor activity in vivo, promoting tumor cell apoptosis.
  • Transcriptomic analysis suggested SLC33A1 as a potential molecular target for annonacin in HCC.

Conclusions:

  • Annonacin from Annona montana exhibits synergistic antitumor activity with sorafenib against advanced HCC.
  • Annonacin may act by reducing ATP levels, promoting apoptosis, and potentially targeting SLC33A1.
  • Annonacin represents a promising candidate for combination therapy in advanced HCC treatment.

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