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

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 osteo...

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Published in:Biomedicine & pharmacotherapy 2018-07, Vol.103, p.1035-1042
Main Authors: Zhao, Yu-Feng, Jiang, Feng, Liang, Xiang-Yan, Wei, Lan-Lan, Zhao, Yan-Yan, Ma, Qiong, Hu, Yun-Sheng, Su, Xing-Li
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Bone Neoplasms - drug therapy
Bone Neoplasms - pathology
Cell death
Cell Line, Tumor
Cell Survival - drug effects
Dose-Response Relationship, Drug
Grifolic acid
Humans
Male
Membrane Potential, Mitochondrial - drug effects
Mice, Nude
Mitochondria
Osteosarcoma
Osteosarcoma - drug therapy
Osteosarcoma - pathology
Sesterterpenes - pharmacology
Sesterterpenes - therapeutic use
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2018.04.132