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Theaflavin-Containing Black Tea Extract: A Potential DNA Methyltransferase Inhibitor in Human Colon Cancer Cells and
Ritwija Bhattacharya1, Ranodeep Chatterjee2, Abul Kalam Azad Mandal3
1Department of Environmental Science, University of Calcutta, Kolkata, India.
Abstract:
Tea is the most popularly consumed beverage in the world. Theaflavin and thearubigins are the key bioactive compounds of black tea that have anticarcinogenic properties as reported in several studies. However, the epigenetic potential of these compounds has not yet been explored. DNA methyltransferase (DNMT) enzymes induce methylation of DNA at cytosine residues and play a significant role in epigenetic regulation and cancer therapy. The present study has explored the role of black tea as a DNMT inhibitor in the prevention of cancer. Herein, the effect of theaflavin has been studied in colon cancer cell line (HCT-116) and EAC-induced solid tumors in mice. It was found that theaflavin prevented cell proliferation and inhibited tumor progression as well. In silico study showed that theaflavin interacted with DNMT1 and DNMT3a enzymes and blocked their activity. Theaflavin also decreased DNMT activity In Vitro and In Vivo as evident from the DNMT activity assay. Results of immunohistochemistry revealed that theaflavin reduced DNMT expression in the tumors of mice. Taken together, our findings showed that theaflavin has a potential role as a DNMT inhibitor in HCT-116 cell line and EAC induced solid tumors in mice.
Insights
Black tea compound theaflavin acts as a DNA methyltransferase (DNMT) inhibitor, potentially preventing cancer. Studies show theaflavin inhibits cancer cell proliferation and tumor growth by blocking DNMT enzymes.
Area of Science:
- Epigenetics
- Cancer Biology
- Pharmacology
Background:
- Black tea contains bioactive compounds like theaflavin with known anticarcinogenic properties.
- Epigenetic regulation, particularly DNA methylation by DNA methyltransferases (DNMTs), is crucial in cancer development and therapy.
- The epigenetic potential of black tea compounds, specifically as DNMT inhibitors, remains largely unexplored.
Purpose of the Study:
- To investigate the role of black tea, specifically theaflavin, as a DNA methyltransferase (DNMT) inhibitor for cancer prevention.
- To evaluate the effect of theaflavin on colon cancer cell proliferation and tumor progression in vivo.
- To explore the molecular mechanisms by which theaflavin might exert its anti-cancer effects through DNMT inhibition.
Main Methods:
- In silico molecular docking studies to assess the interaction of theaflavin with DNMT1 and DNMT3a enzymes.
- In vitro and in vivo DNMT activity assays to quantify the inhibitory effect of theaflavin.
- In vitro studies using the HCT-116 colon cancer cell line to assess cell proliferation.
- In vivo studies using EAC-induced solid tumors in mice to evaluate tumor progression and DNMT expression via immunohistochemistry.
Main Results:
- Theaflavin demonstrated significant inhibition of colon cancer cell proliferation and tumor progression in a mouse model.
- In silico analysis revealed that theaflavin effectively interacts with and blocks the activity of DNMT1 and DNMT3a.
- In vitro and in vivo assays confirmed that theaflavin decreases overall DNMT activity.
- Immunohistochemistry results showed a reduction in DNMT expression within the tumors of mice treated with theaflavin.
Conclusions:
- Theaflavin possesses significant potential as a DNA methyltransferase (DNMT) inhibitor.
- These findings suggest that theaflavin could be a promising agent for cancer prevention and therapy by targeting epigenetic mechanisms.
- The study supports the role of theaflavin in inhibiting cancer cell proliferation and tumor growth through DNMT pathway modulation.
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