Dual roles of demethylation in cancer treatment and cardio-function recovery

Area of Science:

• Biochemistry
• Oncology
• Cardiology

Background:

• Current therapies lack simultaneous tumor inhibition and cardiac repair strategies.
• Demethylation is identified as a common factor in cancer treatment and cardiac repair targets.
• DNA methyltransferase 1 (DNMT1) is a key regulator of methylation processes.

Purpose of the Study:

• To identify novel therapeutic agents with dual anti-cancer and cardio-protective effects.
• To investigate the role of demethylation in cancer and cardiac function.
• To explore dioscin as a potential DNMT1 inhibitor.

Main Methods:

• Screening of a natural compound library to identify DNMT1 inhibitors.
• In vitro assays to assess dioscin's effect on DNMT activity and cancer cell growth.
• RNA-sequencing (RNA-seq) and Methylated DNA immunoprecipitation sequencing (MeDIP-seq) to analyze gene expression and demethylation.
• In vivo studies using Nrf2 knockout mice and tumor-bearing mice with hypertrophy.

Main Results:

• Dioscin was identified as a novel DNMT1-targeted agent.
• Dioscin reduced DNMT activity and inhibited breast cancer cell growth.
• Dioscin demethylated antioxidant gene promoters, increasing their expression via NRF2 recruitment.
• Dioscin demonstrated simultaneous tumor growth inhibition and cardiac injury alleviation in vivo.
• The cardio-protective effects of dioscin were dependent on NRF2.

Conclusions:

• Dioscin is a novel demethylation agent with dual anti-cancer and cardio-protective functions.
• Targeting DNMT1 with dioscin offers a promising strategy for treating co-existing cancer and cardiac conditions.
• The findings highlight the therapeutic potential of dioscin in oncology and cardiology.