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

Abstract
Grifolic acid is a natural compound isolated from the fungus Albatrellus confluens. In the present study, we assessed the effects of grifolic acid on human osteosarcoma cells. We found that grifolic acid dose- and time-dependently induced cell death in the U-2 OS, MG-63, Saos-2, and 143B human osteosarcoma cell lines. Grifolic acid decreased osteosarcoma cell mitochondrial membrane potential, ATP production, and cellular NADH levels, but did not impact mitochondrial membrane potential in isolated mitochondria from human osteosarcoma cells. Intratumoral injection of grifolic acid also promoted tumor cell death and prolonged survival in nude mice bearing human osteosarcoma xenografts. Grifolic acid had no obvious toxicity in mice, with no histological changes in liver, kidney, lung, or heart, and no changes in blood cell counts or levels of plasma total protein, alanine aminotransferase, or aspartate aminotransferase. These results show that grifolic acid induces osteosarcoma cell death by inhibiting NADH generation and ATP production without obvious toxicity. Intratumoral injection of grifolic acid may be a promising anti-osteosarcoma therapeutic option in patients.
AuthorsYu-Feng Zhao, Feng Jiang, Xiang-Yan Liang, Lan-Lan Wei, Yan-Yan Zhao, Qiong Ma, Yun-Sheng Hu, Xing-Li Su
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 103 Pg. 1035-1042 (Jul 2018) ISSN: 1950-6007 [Electronic] France
PMID29710661 (Publication Type: Journal Article)
CopyrightCopyright © 2018 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Sesterterpenes
  • grifolic acid
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Bone Neoplasms (drug therapy, pathology)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Membrane Potential, Mitochondrial (drug effects)
  • Mice, Nude
  • Osteosarcoma (drug therapy, pathology)
  • Sesterterpenes (pharmacology, therapeutic use)
  • Xenograft Model Antitumor Assays

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