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Grifolic acid causes osteosarcoma cell death in vitro and in tumor-bearing mice

Yu-Feng Zhao1, Feng Jiang2, Xiang-Yan Liang1

  • 1The institute of Basic Medical Sciences, Xi'an Medical University, Xi'an, 710021, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|May 2, 2018
PubMed

Insights

Grifolic acid, a natural compound, effectively induces osteosarcoma cell death by inhibiting NADH and ATP production. Intratumoral injection shows promise as a safe and effective anti-osteosarcoma therapy in preclinical models.

Area of Science:

  • Natural Products Chemistry
  • Oncology
  • Biochemistry

Background:

  • Osteosarcoma is a primary bone malignancy with limited treatment options.
  • Natural compounds are a source of novel therapeutic agents.
  • Grifolic acid is a compound derived from the fungus Albatrellus confluens.

Purpose of the Study:

  • To investigate the anti-osteosarcoma effects of grifolic acid.
  • To determine the mechanism of action of grifolic acid in osteosarcoma cells.
  • To evaluate the in vivo efficacy and toxicity of grifolic acid.

Main Methods:

  • Assessed grifolic acid's effects on human osteosarcoma cell lines (U-2 OS, MG-63, Saos-2, 143B).
  • Measured mitochondrial membrane potential, ATP production, and NADH levels.
  • Evaluated intratumoral injection in nude mice bearing osteosarcoma xenografts.
  • Conducted toxicity assessments in mice (histopathology, blood counts, plasma biochemistry).

Main Results:

  • Grifolic acid induced dose- and time-dependent cell death in multiple osteosarcoma cell lines.
  • It decreased cellular mitochondrial membrane potential, ATP production, and NADH levels.
  • Intratumoral injection promoted tumor cell death and prolonged survival in mice with no significant toxicity observed.

Conclusions:

  • Grifolic acid effectively induces osteosarcoma cell death by inhibiting NADH generation and ATP production.
  • Grifolic acid demonstrates a favorable safety profile in vivo.
  • Intratumoral grifolic acid administration is a potential therapeutic strategy for osteosarcoma.
Keywords:
Cell deathGrifolic acidMitochondriaOsteosarcoma

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