2. Maintaining structural integrity of the mutated p53 molecule The functioning of p53 protein is completely dependent upon maintaining the correct three-dimensional conformation of the molecule. Pfizer research 3 has conducted studies in which they inserted small synthetic molecules into the DNA binding region of mutated p53 protein. This technique stabilized the active conformation of newly synthesized mutated p53, but could not rescue p53 if it had already lost the active conformation. With time this active fraction accumulates, and has the ability to inhibit tumor growth in mice.
3. Dietary components Green tea has long been shown to have a protective effect against cancer .The active component is epigallocatechin-3-gallate. Likewise, a component of grapes known as resveratrol has been shown to have a protective effect. Studies have shown that these components activate p53, leading to cell-cycle arrest and apoptosis.
A physiological metabolite of Vitamin A known as retinoic acid is widely used for the prevention of non-melanoma skin cancer. A study 5 has shown that retinoic acid acts by increasing the expression of p53 in epidermal cells.
Finally, several selenium compounds (selenomethionine, sodium selenite, methyl-seleninic acid) act by different mechanisms to regulate the activities of p53, including DNA repair or apoptosis. 7
References
1. Bode A, and Dong Z. Post-translational modification of p53 in tumorigenesis. Nature Reviews Cancer. 2004 Oct; 4 (10): 793-805.
2. Culotta E and Koshland D Jr. p53 sweeps through cancer research. Science. 1993 Dec 24; 262: 1958-1961.
3. Foster B, Coffey H, et al. Pharmacological rescue of mutant p53 conformation and function. Science. 1999 Dec 24; 286 (5449): 2507-2510.
4. Harris C and Hollstein M. Clinical implications of the p53 tumor-suppressor gene. New England J Medicine 1993 Oct 28; 329: 1318-1327.
