Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer
Journal
Fitoterapia
Journal Volume
114
Pages
81-91
Date Issued
2016
Author(s)
Chen, Su-Yu
Shi, YC
YA-WEN CHANG
Liao, VH
Chang, Chao-Lin
Pan, TM.
Chen, Teng-Hai
Chang, Ya-Wen
Lin, Shwu-Bin
Abstract
Three pentacyclic triterpene dilactones were isolated from the fruiting bodies of Ganoderma colossum, a medicinal mushroom. Colossolactone H (colo H) as a new compound and the most cytotoxic among the isolates was studied for its anticancer mechanism and the potential use in cancer therapy. Gene expression profiling analysis indicated that treatment of lung cancer cells with colo H caused upregulation of 252 genes and downregulation of 398 genes. Gene ontology enrichment analysis indicated that the downregulated genes were the most significantly enriched in cell cycle progression, and the upregulated genes were significantly enriched in metabolic process, cellular response to stimulus, and oxidation reduction. Accordingly, colo H was found to halt cell growth and induce cell apoptosis via the elevation of cellular reactive oxygen species to cause DNA damage and the increase of tumor suppressor p53 protein. These events facilitate additive cytotoxicity of colo H and gefitinib for gefitinib-resistant H1650 lung cancer cells. Furthermore, combination of colo H and gefitinib effectively inhibited the growth of tumor xenografts in athymic mice. In addition to the efficacy in adjunctive cancer therapy, we have also demonstrated the isolation of colo H from cultivated G. colossum. Thus it is feasible to use colo H or Ganoderma colossum for cancer therapy. ? 2016
Subjects
Colossolactone; Complementary medicine; Cytotoxicity; Ganoderma colossum; Oxidative damage; Triterpene dilactone
SDGs
Other Subjects
colossolactone G; colossolactone H; cytotoxic agent; doxorubicin; gefitinib; pentacyclic triterpene; protein p53; reactive oxygen metabolite; schisanlactone A; transcription factor Nrf2; unclassified drug; antineoplastic agent; colossolactone H; gefitinib; protein p53; quinazoline derivative; reactive oxygen metabolite; triterpene; absorption; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; apoptosis assay; Article; cancer cell; cancer inhibition; cancer therapy; cell cycle progression; cell viability assay; circular dichroism; controlled study; DNA damage; down regulation; drug efficacy; drug isolation; drug potentiation; Fenton reaction; Ganoderma; Ganoderma colossum; gene expression profiling; gene expression regulation; gene ontology; heteronuclear multiple bond correlation; heteronuclear single quantum coherence; human; human cell; IC50; immunoblotting; immunofluorescence; lung cancer; male; medicinal mushroom; mouse; nonhuman; nuclear Overhauser effect; oxidation reduction reaction; priority journal; proton nuclear magnetic resonance; real time polymerase chain reaction; stereochemistry; tumor volume; tumor xenograft; upregulation; animal; Bagg albino mouse; chemical structure; chemistry; drug effects; drug screening; Ganoderma; isolation and purification; lung tumor; metabolism; tumor cell line; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; DNA Damage; Down-Regulation; Ganoderma; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Quinazolines; Reactive Oxygen Species; Triterpenes; Tumor Suppressor Protein p53; Up-Regulation; Xenograft Model Antitumor Assays
Type
journal article