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.

Ergosterol peroxide activates Foxo3-mediated cell death signaling by inhibiting AKT and c-Myc in human hepatocellular carcinoma cells

“…Further study found that the Ganoderma oil could induce death of cancer stem-like cells [11]. We purified the bioactive components and finally isolated the single molecule ergosterol peroxide from this medicinal mushroom.…”

“…We purified the bioactive components and finally isolated the single molecule ergosterol peroxide from this medicinal mushroom. We found that ergosterol peroxide could stimulate cell death of a panel of cancer cells including human hepatocellular carcinoma cells HepG2 [11]. Erogosterol peroxide is a member of a class of fungal secondary metabolites of 5α, 8α-endoperoxide sterol derivatives.…”

MiR-378 Promotes the Migration of Liver Cancer Cells by Down-Regulating Fus Expression

“…Additionally, some miRNAs, such as miR-378, are over-expressed in diverse cancers and seem to function as oncogenes [15,25,26,27,28]. Previous studies have indicated that miR-378 can promote cell survival, tumor growth, and angiogenesis in glioblastoma cells [26].…”

Anti-cancer drugs for cardioprotection

“…Our previous study unraveled that ergosterol peroxide isolated from Ganoderma lucidum induced cell death by abolishing microRNA miR-378-mediated tumor cells on chemoresistance. 6 In addition to microRNAs, our recent study also validated that the cardioprotective effect of Ganoderma lucidum is mediated by a circular RNA circ-Foxo3 encoded by the Foxo3 gene. 2 Increased expression of circ-Foxo3 RNA has also been found in mice with reduced cardiac function.…”