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Discovery of Green Tea Polyphenol-Based Antitumor Drugs: Mechanisms of Action and Clinical Implications

Abstract

Green tea polyphenols, especially catechins, have shown great promise for use as anticancer agents. One such catechin, epigallocatechin-3 gallate (EGCG), is of particular interest due to mounting evidence of its ability to interrupt a variety of essential signaling pathways in cancer cells and target multiple tumor-specific proteins, and its synergistic effects when paired with commonly used anticancer therapies. However, EGCG has a number of disadvantages, e.g., low stability and poor bioavailability, as well as rapid metabolic transformations in vivo. We previously developed a prodrug of EGCG (Pro-EGCG or 1) which shows increased levels of stability, bioavailability, and biological activity in human cancer cells and xenografts as compared to EGCG. In order to potentially reduce the susceptibility of EGCG analogs to be methylated and thus inhibited by catechol-O-methyltransferase (COMT), we synthesized novel analogs and prodrugs where one or two hydroxyl or acetoxy groups, respectively, have been removed from the gallate ester moiety. Such prodrugs (2a and 4a) were reported recently to have potent antiproliferative, antiangiogenic, and antifibrotic properties. We previously also reported that synthetic EGCG analogs 4 and 6 were more potent AMPK activators than metformin and EGCG. Here we review the activity of 4 and 6 in inhibiting growth of uterine fibroid cells. We also review the potential of these novel EGCG analogs and prodrugs as anticancer drugs and discuss the potential mechanisms of action involved.

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Acknowledgments

Partially supported by Canadian Institutes of Health Research (CIHR).

Conflicts of interest: T.H.C., Q.P.D., and R.F. are the named inventors of patents and patent applications; other authors declare no conflicts of interest.

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Correspondence to Q. Ping Dou .

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Ahmed, R.S.I. et al. (2019). Discovery of Green Tea Polyphenol-Based Antitumor Drugs: Mechanisms of Action and Clinical Implications. In: Joshee, N., Dhekney, S., Parajuli, P. (eds) Medicinal Plants. Springer, Cham. https://doi.org/10.1007/978-3-030-31269-5_14

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