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Published on: October 27, 2020
Epigallocatechin-3-gallate suppressed breast oncogenesis via the miR-27a/Wnt/β-catenin pathway axis
Shrila Banerjee1, Abul Kalam Azad Mandal1
1Department of Biotechnology, School of BioSciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Introduction:
Breast cancer is a global health concern with increased chemotherapeutic side effects and escalated chemoresistance, requiring alternative therapies. Epigallocatechin-3-gallate (EGCG), a bioactive green tea polyphenol, has exhibited promising anticancer properties. Our study aimed to investigate the tumour-suppressive effect of EGCG and its mechanism in breast cancer.
Method:
Anticancer activities, such as cell viability, migration, cell cycle progression, and apoptosis, were evaluated. To investigate the molecular mechanism, miR-27a-3p expression was compared against EGCG, a miR-27a-3p inhibitor, and a combination of EGCG with miR-27a-3p inhibitor treatments. The influence of the individual miRNA inhibitor and its combination with EGCG on cell proliferation was also evaluated to establish the anticancer activity of EGCG via miR-27a-3p modulation. The effects of the individual miRNA inhibitor, EGCG, and their combination treatments on key Wnt/β-catenin pathway markers were examined to further establish the therapeutic route of EGCG via the miR-27a/Wnt/β-catenin pathway axis.
Result:
EGCG notably decreased cell viability and migration, induced apoptosis, and initiated G0/G1 cell cycle arrest. Therapeutic investigation of EGCG on MDA-MB-231 cells indicated its regulatory role on oncogenic miR-27a-3p, which was confirmed when miR-27a-3p expression was significantly lower in the combination treatment of EGCG and the miR-27a-3p inhibitor than in the individual inhibitor treatment in this study. The anticancer potency of the miR-27a-3p inhibitor was also revealed against MDA-MB-231 cells, supporting miRNA therapeutics against cancer. Furthermore, EGCG-modulated miR-27a-3p affected key Wnt/β-catenin pathway markers, causing signal suppression, including suppression of a key Wnt-targeted gene and the G1 phase regulator cyclin-D1, which also indicated its potential against breast cancer.
Discussion:
These results signify the therapeutic potential of EGCG and its potential implementation through the miR-27a/Wnt/β-catenin pathway axis, resulting in reduced breast cancer proliferation, metastasis, and relapse.
Insights
Epigallocatechin-3-gallate (EGCG) shows promise as a breast cancer therapy by suppressing tumor growth and metastasis. EGCG functions by modulating miR-27a-3p, impacting the Wnt/β-catenin pathway, and reducing cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer presents significant global health challenges, marked by increasing chemotherapeutic side effects and chemoresistance.
- Epigallocatechin-3-gallate (EGCG), a potent polyphenol from green tea, demonstrates notable anticancer properties, necessitating further investigation into its therapeutic mechanisms.
Purpose of the Study:
- To investigate the tumor-suppressive effects of EGCG in breast cancer.
- To elucidate the molecular mechanisms underlying EGCG's anticancer activity, focusing on miR-27a-3p and the Wnt/β-catenin pathway.
Main Methods:
- Evaluated EGCG's impact on breast cancer cell viability, migration, cell cycle, and apoptosis.
- Assessed miR-27a-3p expression levels following treatments with EGCG, a miR-27a-3p inhibitor, and their combination.
- Examined the modulation of key Wnt/β-catenin pathway markers, including cyclin-D1, in response to EGCG treatment.
Main Results:
- EGCG significantly reduced breast cancer cell viability and migration while inducing apoptosis and G0/G1 cell cycle arrest.
- EGCG treatment led to decreased miR-27a-3p expression, confirming its regulatory role.
- EGCG modulated the Wnt/β-catenin pathway, suppressing key markers like cyclin-D1, indicating a potential therapeutic route.
Conclusions:
- EGCG exhibits significant therapeutic potential against breast cancer.
- The anticancer effects of EGCG are mediated through the miR-27a/Wnt/β-catenin pathway.
- EGCG holds promise for reducing breast cancer proliferation, metastasis, and relapse.
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