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Published on: September 30, 2016
Tetranectin targeting by epigallocatechin gallate suppresses colon cancer cell proliferation
Sana Iram1, Safikur Rahman2, Shahid Ali1
1Department of Medical Biotechnology and Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Abstract:
Tetranectin is a serum protein that binds to plasminogen and enhances its proteolytic activation, which underlies the involvement of tetranectin in the development of several carcinomas including colon cancer. In the present study, structure-based in silico screening of natural products showed that epigallocatechin gallate with anticancer effects binds to tetranectin. Binding to epigallocatechin gallate to tetranectin was confirmed by intrinsic fluorescence quenching assays and isothermal titration calorimetry. Furthermore, epigallocatechin gallate efficiently inhibited the activity of tetranectin to enhance the activation of plasminogen. We also found that tetranectin enhanced the proliferation of CT-26 colon cancer cells. Epigallocatechin gallate showed its cytotoxic effect on CT-26 cells due to its binding to tetranectin and the consequent suppression of the cell proliferation. These results demonstrate that the anticancer effect of epigallocatechin gallate is mediated, at least in part, by inhibiting tetranectin as a binding target.
Insights
Epigallocatechin gallate, a natural compound, inhibits tetranectin, a protein linked to colon cancer progression. This interaction suppresses cancer cell proliferation, highlighting a novel therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Tetranectin is a serum protein implicated in the development of various carcinomas, including colon cancer.
- Tetranectin facilitates the proteolytic activation of plasminogen, contributing to cancer progression.
Purpose of the Study:
- To investigate the potential of natural products to inhibit tetranectin's function.
- To explore epigallocatechin gallate as a therapeutic agent targeting tetranectin in colon cancer.
Main Methods:
- Structure-based in silico screening of natural products for tetranectin binding.
- Confirmation of epigallocatechin gallate-tetranectin binding using intrinsic fluorescence quenching and isothermal titration calorimetry.
- Assessment of epigallocatechin gallate's effect on tetranectin-mediated plasminogen activation and CT-26 colon cancer cell proliferation.
Main Results:
- Epigallocatechin gallate was identified as a natural product that binds to tetranectin.
- Binding was experimentally confirmed, and epigallocatechin gallate demonstrated inhibition of tetranectin's enhancement of plasminogen activation.
- Tetranectin was shown to promote CT-26 colon cancer cell proliferation; epigallocatechin gallate suppressed this proliferation by inhibiting tetranectin.
Conclusions:
- Epigallocatechin gallate exhibits anticancer effects against colon cancer cells by targeting tetranectin.
- Inhibition of tetranectin by epigallocatechin gallate is a key mechanism underlying its cytotoxic activity.
- Tetranectin represents a potential therapeutic target for colon cancer treatment, with epigallocatechin gallate as a promising modulator.
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