M. M. Aldajani1, C. N. Vanicek1, N. Alhazzaa1, R. Agarwal1, J. P. Geibel1 1Yale University School Of Medicine,Surgery,New Haven, CT, USA
Introduction:
Colorectal cancer remains one of the leading causes of death in the United States and worldwide. Although early screening has played an important role in improving clinical outcomes resulting in a reduced death rate. There remain opportunities to develop new therapeutic agents and strategies to further improve survival odds. In this regiment of new methodologies one can look at agents that can also be taken prophylactically to reduce the risk of tumor formation. Typically for cancer to grow and invade healthy tissues, it must maintain a higher (more alkali) intracellular pH and a lower (more acidic) extracellular pH, in the immediate environment around the metaplastic cell. This leads to volume changes within the tumor and to destruction of the surrounding cells thereby aiding the tumor to expand in size. Recently there is evidence the chronic exposure to Vitamin C may lead to a reduction in tumor formation in the colon. In the present study we examined what acid base transport proteins are modulated by acute exposure to Vitamin C that result in enhanced proton extrusion, and elevation in intracellular pH.
Methods:
Following excision, rat colon was digested leaving single isolated crypts, which were then incubated with the pH sensitive dye BCECF. The crypts were then imaged while being perfused with solutions either containing or devoid of Vitamin C. The ratio image data was collected every 15 second to allow a direct real time measurement of the effects of Vitamin C on colonic hydrogen ion transport.
Results:Acute exposure to Vitamin C lead to a reduction in Na-dependent H ion extrusion (NHE). The effects of Vitamin C were dose dependent. In a separate series of studies, we investigated the role of glucose in the effect of Vitamin C. Removal of glucose from the solutions or addition of phlorizine had no effect on the Vitamin C of NHE activity.
Conclusion:
We found that acute exposure to Vitamin C can reduce NHE activity and that this effect is not glucose dependent. Our results show an important role for Vitamin C as an antitumorigenic agent under acute conditions. The glucose independence makes this an important nutraceutical therapy that can be use both in nondiabetic and diabetic patients.