[Frontiers in Bioscience S4, 300-320, January 1, 2012]

Operation 'p53 Hunt' to combat cancer: Theaflavins in action

Suchismita Mohanty1, Arghya Adhikary1, Samik Chakrabarty1, Gaurisankar Sa1, Tanya Das1

1Division of Molecular Medicine, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata, India

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Theaflavins leading the anti-cancer operation
4. p53: The guardian of genome
4.1. Wild-type p53 'handcuffs' Cancer
4.1.2. Tumor metabolism: p53 empties the fuel tank
4.1.3. Angiogenesis: p53 blocks fuel supply
4.1.4. Metastasis: p53 halts the race
4.1.5. Apoptosis: p53 bringing the end nearer
4.1.6. Drug resistance and cancer therapeutics: p53 overcomes the challenge
4.2. Inactivation impairs wild-type p53 functions
4.3. Mutant p53: When the savior becomes the slayer
4.3.1. Mutant p53 sustains energy
4.3.2. Mutant p53 supplies fuel in excess
4.3.3. Mutant p53 accelerates the race
4.3.4. Mutant p53 overpowers death
4.3.5. Mutant p53 strengthens drug resistance
5. Theaflavins exploit p53 during the anti-cancer operation
5.1. Theaflavins targeting wild-type p53
5.1.1. Depriving of currency for growth
5.1.2. Inhibiting nutrient supply
5.1.3. Halting the parade
5.1.4. Targeting the absence
5.1.5. Overpowering disobedience
5.2. Theaflavins in absence of wild-type p53
6. Cancer stem cells: p53 breaking down tumor's engine
7. Can theaflavins up root the 'root of all evils' by targeting p53? : A hypothesis
8. Concluding remarks
9. Acknowledgment
10. References

1. ABSTRACT

With phytochemicals executing a plethora of anti-tumor mechanisms, targeting the 'guardian angel' p53 appears to be a critical strategy to energize the process of cancer therapeutics. Regulation of anti-tumor p53 functions by dietary plant polyphenols particularly black tea and its active component theaflavins has gained immense recognition from the point of view of both efficacy and safety. This review highlights the complexities of p53 functions, molecular mechanisms of its inactivation in cancer, and therapeutic strategies for rescuing p53 dysfunction in tumors using theaflavins. It describes how theaflavins, by steering a single molecular target - p53, regulate multiple hallmarks of carcinogenesis i.e., tumor glycolysis, angiogenesis, metastasis, apoptosis and drug resistance. Additionally, considering the rising of the current concept of cancer stem cells (CSCs), the sole participant in tumor evolution, the review discusses about the possible role of theaflavin-p53 cross talk in targeting CSCs. Such attempts to target the complexities of p53 functions during neogenesis will be of immense help in developing a "new" strategy for successful cancer prevention and therapy by theaflavins.