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

  • Reda Saber Ibrahim Ahmed
  • Claire Soave
  • Tracey Guerin Edbauer
  • Kush Rohit Patel
  • Yasmine Elghoul
  • Antonio Vinicius Pazetti de Oliveira
  • Andrea Renzetti
  • Robert Foldes
  • Tak-Hang Chan
  • Q. Ping DouEmail author
Chapter

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.

Keywords

Green tea Polyphenols EGCG EGCG analogs EGCG prodrugs COMT Molecular targeting Cancer therapy 

Notes

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Reda Saber Ibrahim Ahmed
    • 1
    • 2
    • 3
    • 4
    • 5
  • Claire Soave
    • 1
    • 2
    • 3
    • 4
  • Tracey Guerin Edbauer
    • 1
    • 2
    • 3
    • 4
  • Kush Rohit Patel
    • 1
    • 2
    • 3
    • 4
  • Yasmine Elghoul
    • 1
    • 2
    • 3
    • 4
  • Antonio Vinicius Pazetti de Oliveira
    • 1
    • 2
    • 3
    • 4
    • 6
  • Andrea Renzetti
    • 7
  • Robert Foldes
    • 8
  • Tak-Hang Chan
    • 7
    • 9
  • Q. Ping Dou
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Barbara Ann Karmanos Cancer Institute, School of MedicineWayne State UniversityDetroitUSA
  2. 2.Department of Oncology, School of MedicineWayne State UniversityDetroitUSA
  3. 3.Department of Pharmacology, School of MedicineWayne State UniversityDetroitUSA
  4. 4.Department of Pathology, School of MedicineWayne State UniversityDetroitUSA
  5. 5.Pharmacology Department, Faculty of Veterinary MedicineSouth Valley UniversityQenaEgypt
  6. 6.Department of Physiology, School of MedicinePontifical Catholic University of Sao PauloSorocabaBrazil
  7. 7.Department of ChemistryMcGill UniversityMontrealCanada
  8. 8.Viteava Pharmaceuticals Inc.TorontoCanada
  9. 9.Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug DiscoveryHong Kong Polytechnic UniversityHong Kong SARChina

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