title: Elimination of quiescent slow-cycling cells via reducing quiescence depth by natural compounds purified from Ganoderma lucidum.
abstract: The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit. Accordingly, we showed that quiescent breast cancer cells (MCF7), compared to its non-transformed counterpart (MCF10A), were preferentially killed by ergosterol peroxide and ganodermanondiol treatment presumably due to their already less stable quiescent state. The cytotoxic effect of natural Ganoderma lucidum compounds against quiescent cells, preferentially on quiescent cancer cells vs. non-cancer cells, may help future antitumor development against the slow-cycling cancer cell subpopulations including cancer stem and progenitor cells.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.|Jiangsu Academy of Agricultural sciences, Nanjing, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Miller
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Everetts
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy and Fujian Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Fujian Xianzhilou Biological Science and Technology Co, Ltd, Fuzhou, Fujian, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy and Fujian Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.|Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Yao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D020940:Reishi
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; C050246:ganodermadiol; D007810:Lanosterol; C036071:ergosterol-5,8-peroxide; D004875:Ergosterol
keywords: cancer stem cells; ganoderma lucidum; natural compounds; quiescence; slow-cycling cells