title: Ergosterol peroxide isolated from Ganoderma lucidum abolishes microRNA miR-378-mediated tumor cells on chemoresistance.
abstract: Due to an altered expression of oncogenic factors and tumor suppressors, aggressive cancer cells have an intrinsic or acquired resistance to chemotherapeutic agents. This typically contributes to cancer recurrence after chemotherapy. microRNAs are short non-coding RNAs that are involved in both cell self-renewal and cancer development. Here we report that tumor cells transfected with miR-378 acquired properties of aggressive cancer cells. Overexpression of miR-378 enhanced both cell survival and colony formation, and contributed to multiple drug resistance. Higher concentrations of chemotherapeutic drugs were needed to induce death of miR-378-transfected cells than to induce death of control cells. We found that the biologically active component isolated from Ganoderma lucidum could overcome the drug-resistance conferred by miR-378. We purified and identified the biologically active component of Ganoderma lucidum as ergosterol peroxide. We demonstrated that ergosterol peroxide produced greater activity in inducing death of miR-378 cells than the GFP cells. Lower concentrations of ergosterol peroxide were needed to induce death of the miR-378-transfected cells than in the control cells. With further clinical development, ergosterol peroxide represents a promising new reagent that can overcome the drug-resistance of tumor cells.
authors.affiliation: State Key Laboratory of Applied Microbiology in South China (Ministry-Guangdong Province Jointly Breeding Base), and Guangdong Institute of Microbiology, Guangzhou, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Wu
authors.forename: Yi-Zhen
authors.initials: YZ
authors.lastname: Xie
authors.forename: Zhaoqun
authors.initials: Z
authors.lastname: Deng
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Li
authors.forename: Weining
authors.initials: W
authors.lastname: Yang
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Jiao
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.forename: Sen-Zhu
authors.initials: SZ
authors.lastname: Li
authors.forename: Hong-Hui
authors.initials: HH
authors.lastname: Pan
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Yee
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Lee
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020940:Reishi / Q000737:chemistry*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D003561:Cytarabine; C036071:ergosterol-5,8-peroxide; D008727:Methotrexate; D004875:Ergosterol