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2-Hydroxy-3-methylanthraquinone inhibits homologous recombination repair in osteosarcoma through the MYC-CHK1-RAD51

Doudou Jing1,2, Xuanzuo Chen2, Zhenhao Zhang2

  • 1Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.

Molecular Medicine (Cambridge, Mass.)
|January 30, 2023
PubMed
Abstract

Insights

2-Hydroxy-3-methylanthraquinone (HMA) inhibits osteosarcoma growth and DNA repair by targeting the MYC-CHK1-RAD51 pathway. This Chinese medicine offers a potential low-toxicity strategy for osteosarcoma treatment, bypassing chemotherapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma, a bone cancer common in adolescents, exhibits enhanced DNA damage response (DDR), limiting chemotherapy efficacy.
  • Targeting DDR is a promising strategy, but existing inhibitors have significant side effects.
  • Chinese herbal medicines, like 2-Hydroxy-3-methylanthraquinone (HMA), show anti-tumor potential with lower toxicity.

Purpose of the Study:

  • To investigate the anti-osteosarcoma effects of HMA.
  • To elucidate the molecular mechanisms underlying HMA's anti-cancer activity in osteosarcoma.
  • To explore HMA as a potential therapeutic agent for osteosarcoma.

Main Methods:

  • Cell proliferation, metastasis, and apoptosis were assessed using CCK-8, colony formation, transwell, and flow cytometry assays.
  • Molecular mechanisms were explored via RNA-sequencing, Western blotting, immunofluorescence, and CHIP assays.
  • The roles of MYC, CHK1, and RAD51 in HMA's effects were confirmed through rescue and RNA interference experiments.

Main Results:

  • HMA significantly inhibited osteosarcoma cell proliferation and metastasis.
  • HMA impairs homologous recombination repair by downregulating the MYC-CHK1-RAD51 pathway, mediated by the PI3K/AKT signaling pathway.
  • RNA-seq and molecular assays confirmed the interaction between MYC, CHK1, and RAD51 under HMA treatment.

Conclusions:

  • HMA effectively inhibits osteosarcoma proliferation and DNA repair via the MYC-CHK1-RAD51 axis, modulated by PI3K-AKT signaling.
  • This study reveals HMA's molecular mechanism against osteosarcoma.
  • HMA presents a potential therapeutic strategy for osteosarcoma, offering an alternative to conventional chemotherapy.
Keywords:
2-Hydroxy-3-methylanthraquinoneCHK1DNA damage response (DDR)MYCRAD51

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