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PMID: 22952996 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ergosterol peroxide isolated from Ganoderma lucidum abolishes microRNA miR-378-mediated tumor cells on chemoresistance.

PloS one ·Vol. 7 ·No. 8 ·2012-00-00 ·Pages e44579

Wu QP, Xie YZ, Deng Z, Li XM, Yang W, Jiao CW, Fang L, Li SZ, Pan HH, Yee AJ, Lee DY, Li C, Zhang Z, Guo J, Yang BB

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.

MeSH Terms
Antineoplastic Agents/chemistry,isolation & purification,pharmacology Cell Death/drug effects Cell Line, Tumor Cell Survival/drug effects Ceramides/pharmacology Cytarabine/pharmacology Drug Resistance, Neoplasm/drug effects,genetics Drug Screening Assays, Antitumor Ergosterol/analogs & derivatives,isolation & purification,pharmacology Humans Methotrexate/pharmacology MicroRNAs/genetics,metabolism Reishi/chemistry Transfection
Chemicals
Antineoplastic Agents Ceramides MIRN378 microRNA, human MicroRNAs Cytarabine ergosterol-5,8-peroxide Methotrexate Ergosterol
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Wu Qing-Ping
State Key Laboratory of Applied Microbiology in South China (Ministry-Guangdong Province Jointly Breeding Base), and Guangdong Institute of Microbiology, Guangzhou, China.
Xie Yi-Zhen
Deng Zhaoqun
Li Xiang-Min
Yang Weining
Jiao Chun-Wei
Fang Ling
Li Sen-Zhu
Pan Hong-Hui
Yee Albert J
Lee Daniel Y
Li Chong
Zhang Zhi
Guo Jun
Yang Burton B
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0044579
Published
2012-00-00
Epub
2012-00-30
Pages
e44579
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3431381
Subset
IM
Grants
Canadian Institutes of Health Research · MOP-102635 · Canada
Canadian Institutes of Health Research · MOP-111171 · Canada
External Links
PubMed source DOI: 10.1371/journal.pone.0044579 PMC Full Text View journal details
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