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Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer
Hyunkyung Lee1, Seungyeon Lee1, Dawoon Jeong1
1Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
Background:
Ginsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes.
Methods:
The effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2.
Results:
LINE1 showed induction of hypomethylation at specific CpGs by 1.6-9.1% (p < 0.05). Genome-wide methylation analysis identified the "cell-mediated immune response"-related pathway as the top network. Cell proliferation of MCF-7 was retarded by Rh2 in a dose-dependent manner. Hypermethylated genes such as CASP1, INSL5, and OR52A1 showed downregulation in the Rh2-treated MCF-7, while hypomethylated genes such as CLINT1, ST3GAL4, and C1orf198 showed upregulation. Notably, a higher survival rate was associated with lower expression of INSL5 and OR52A1 in breast cancer patients, while with higher expression of CLINT1.
Conclusion:
The results indicate that Rh2 induces epigenetic methylation changes in genes involved in immune response and tumorigenesis, thereby contributing to enhanced immunogenicity and inhibiting the growth of cancer cells.
Insights
Ginsenoside Rh2 alters DNA methylation in breast cancer cells, impacting immune response and tumor growth pathways. This epigenetic modification by Rh2 may enhance cancer immunogenicity and inhibit proliferation.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Research
Background:
- Ginsenoside Rh2 is known to modulate immune cell activity and inhibit tumor cell growth.
- The epigenetic regulation, specifically DNA methylation changes, by Rh2 in cancer cells remains largely unexplored.
- Comprehensive approaches are needed to detect methylation alterations induced by Rh2.
Purpose of the Study:
- To investigate the genome-wide DNA methylation changes induced by Ginsenoside Rh2 in breast cancer cells.
- To identify specific genes and signaling pathways epigenetically regulated by Rh2.
- To correlate these epigenetic changes with cellular effects like proliferation and apoptosis.
Main Methods:
- Treatment of MCF-7 breast cancer cells with Ginsenoside Rh2.
- Pyrosequencing analysis of the global methylation marker LINE1.
- Genome-wide methylation analysis to identify differentially methylated genes and pathways.
- Monitoring of apoptosis and cell proliferation rates.
Main Results:
- Rh2 induced LINE1 hypomethylation at specific CpGs (1.6-9.1%).
- Genome-wide analysis revealed "cell-mediated immune response" as a top affected pathway.
- Rh2 dose-dependently inhibited MCF-7 cell proliferation.
- Hypermethylated genes (CASP1, INSL5, OR52A1) were downregulated, while hypomethylated genes (CLINT1, ST3GAL4, C1orf198) were upregulated.
- Gene expression patterns of INSL5, OR52A1, and CLINT1 correlated with patient survival.
Conclusions:
- Ginsenoside Rh2 induces significant epigenetic methylation changes in breast cancer cells.
- These methylation alterations affect genes involved in immune response and tumorigenesis.
- Rh2's epigenetic effects contribute to enhanced cancer immunogenicity and inhibited tumor growth.
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