Quercetin downregulates the expression of IL15 in cancer cells through DNA methylation
1Shanghai Key Laboratory of Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai, China. hxwang@cemps.ac.cn.
Objective:
This study aimed to investigate the effect of quercetin on cellular immunity (via IL15 expression) against cancer and to elucidate its regulatory mechanism.
Materials And Methods:
HeLa cells and A549 cells were cultured in vitro and were divided into control (DMSO treated) and experimental groups (treated with different concentrations of quercetin). Transcript levels of IL15 and DNA methyltransferase (DNMTS) were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Genomic DNA was extracted, treated with bisulfite, and the promoter region of IL15 was cloned. Finally, Sanger sequencing was used to detect the degree of promoter methylation.
Results:
Following quercetin treatment, the expression of IL15 was significantly downregulated in HeLa and A549 cells. The methylation level of IL15 promoter in HeLa cells was about twice that of the control group, and the methylation level of IL15 promoter in A549 cells was about three times that of the control group.
Conclusions:
Quercetin inhibits cancer cell proliferation while downregulating IL15 expression, and this regulation is achieved by increasing the methylation of the IL15 promoter.
Insights
Quercetin inhibits cancer cell proliferation by downregulating Interleukin-15 (IL15) expression. This effect is mediated by increased methylation of the IL15 promoter region, impacting cellular immunity.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Cellular immunity plays a crucial role in cancer surveillance.
- Interleukin-15 (IL15) is a key cytokine involved in immune responses against cancer.
- Quercetin is a natural compound with potential anti-cancer properties.
Purpose of the Study:
- To investigate the impact of quercetin on cellular immunity, specifically IL15 expression, in cancer cells.
- To elucidate the molecular mechanism by which quercetin affects IL15 expression.
- To determine if quercetin influences the methylation status of the IL15 promoter.
Main Methods:
- In vitro culture of HeLa and A549 cancer cell lines.
- Treatment with varying concentrations of quercetin.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure IL15 and DNA methyltransferase (DNMTs) transcript levels.
- Bisulfite sequencing to analyze IL15 promoter methylation.
Main Results:
- Quercetin treatment led to significant downregulation of IL15 expression in both cell lines.
- IL15 promoter methylation levels increased approximately twofold in HeLa cells and threefold in A549 cells post-quercetin treatment.
- A correlation was observed between quercetin concentration and increased IL15 promoter methylation.
Conclusions:
- Quercetin exhibits anti-proliferative effects on cancer cells.
- Quercetin downregulates IL15 expression.
- The downregulation of IL15 by quercetin is mediated through epigenetic modification, specifically by increasing the methylation of the IL15 promoter.
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