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Anticarin β Inhibits Human Glioma Progression by Suppressing Cancer Stemness via STAT3

Min Zhang1,2, Zhi Dai1, Xudong Zhao1

  • 1Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology - The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Kunming, China.

Frontiers in Oncology
|August 19, 2021
PubMed

Insights

Anticarin β, a natural compound, effectively suppresses malignant glioma growth and stemness by inducing apoptosis and DNA damage. This compound shows promise as a novel therapeutic agent for brain cancer with minimal toxicity.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Malignant glioma is a prevalent and challenging brain cancer.
  • Glioma stem cells contribute to treatment resistance, relapse, and high tumorigenesis.
  • Targeting glioma stem cells is crucial for effective glioma treatment.

Purpose of the Study:

  • To investigate the efficacy of anticarin β, a natural compound from Antiaris toxicaria, against malignant glioma.
  • To determine if anticarin β can suppress glioma stemness and induce apoptosis.
  • To evaluate the in vivo efficacy and toxicity of anticarin β in a glioma mouse model.

Main Methods:

  • In vitro assessment of anticarin β's effect on glioma cell proliferation and apoptosis.
  • Cell sphere formation assays and gene expression analysis to evaluate stemness.
  • In vivo studies using an orthotopic xenograft mouse model to assess tumor growth inhibition and survival.

Main Results:

  • Anticarin β selectively suppressed glioma cell proliferation and induced apoptosis with significantly lower IC50 compared to normal neural stem cells.
  • Anticarin β inhibited cancer stemness by modulating stemness gene expression.
  • Anticarin β induced DNA damage, regulated oncogenic signaling pathways (STAT3, Akt, MAPKs), inhibited glioma growth, and prolonged survival in mice without systemic toxicity.

Conclusions:

  • Anticarin β demonstrates potent anti-glioma activity by targeting both cancer cells and glioma stem cells.
  • Anticarin β exhibits a favorable safety profile and therapeutic potential.
  • Anticarin β represents a promising candidate for the development of novel malignant glioma therapies.
Keywords:
DNA damageapoptosisgliomanatural productstemness

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