title: Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer.
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.
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
authors: Su-Yu
authors: SY
authors: Chen
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China.
authors: Chao-Lin
authors: CL
authors: Chang
authors: Trineo Biotechnology Co., LTD, New Taipei City, Taiwan, Republic of China.
authors: Teng-Hai
authors: TH
authors: Chen
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China. Electronic address: ywchang364@ntu.edu.tw.
authors: Ya-Wen
authors: YW
authors: Chang
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; Trineo Biotechnology Co., LTD, New Taipei City, Taiwan, Republic of China. Electronic address: sblin@ntu.edu.tw.
authors: Shwu-Bin
authors: SB
authors: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004249:DNA Damage; D015536:Down-Regulation; D032902:Ganoderma / Q000737:chemistry*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D011799:Quinazolines / Q000493:pharmacokinetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D017382:Reactive Oxygen Species; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; C000613546:colossolactone H; D000077156:Gefitinib
keywords: Colossolactone; Colossolactone G (PubChem CID: 10187119); Complementary medicine; Cytotoxicity; Ganoderma colossum; Gefitinib (PubChem CID: 123631); Glutathione (PubChem CID: 124886); Oxidative damage; Triterpene dilactone