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Ergosterol peroxide isolated from Ganoderma lucidum abolishes microRNA miR-378-mediated tumor cells on
Qing-Ping Wu1, Yi-Zhen Xie, Zhaoqun Deng
1State Key Laboratory of Applied Microbiology in South China (Ministry-Guangdong Province Jointly Breeding Base), and Guangdong Institute of Microbiology, Guangzhou, China.
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.
Insights
MicroRNAs like miR-378 can cause aggressive cancer cells to resist chemotherapy. However, ergosterol peroxide from Ganoderma lucidum effectively overcomes this drug resistance, offering a potential new cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Aggressive cancer cells often develop resistance to chemotherapy due to altered oncogene and tumor suppressor expression, leading to recurrence.
- MicroRNAs (miRNAs), regulators of cell renewal and cancer, are implicated in cancer development and drug resistance.
- Tumor cells transfected with miR-378 exhibited characteristics of aggressive cancer cells, including enhanced survival and colony formation.
Purpose of the Study:
- To investigate the role of miR-378 in conferring chemoresistance to cancer cells.
- To identify compounds capable of overcoming miR-378-induced drug resistance.
- To evaluate the potential of Ganoderma lucidum components as therapeutic agents against drug-resistant cancers.
Main Methods:
- Transfection of tumor cells with miR-378 mimic.
- Assessment of cell survival, colony formation, and response to chemotherapeutic agents in miR-378-transfected cells.
- Isolation, purification, and identification of active compounds from Ganoderma lucidum.
- Testing the efficacy of isolated compounds in overcoming miR-378-mediated drug resistance.
Main Results:
- Overexpression of miR-378 significantly enhanced cancer cell survival, colony formation, and acquired multiple drug resistance.
- Higher concentrations of chemotherapeutic drugs were required to induce cell death in miR-378-transfected cells compared to controls.
- Ergosterol peroxide, isolated from Ganoderma lucidum, effectively overcame miR-378-induced drug resistance.
- Lower concentrations of ergosterol peroxide were needed to induce death in miR-378-transfected cells than in control cells.
Conclusions:
- miR-378 plays a crucial role in promoting aggressive cancer cell phenotypes and conferring resistance to chemotherapy.
- Ergosterol peroxide from Ganoderma lucidum demonstrates significant potential in overcoming miRNA-mediated drug resistance in cancer.
- Ergosterol peroxide represents a promising therapeutic candidate for clinical development to combat chemoresistant tumors.
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