Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation

Abstract

Background/Aim: Colorectal cancer is still considered a leading cause of death in the United States and worldwide. One potential way to improve survival besides detection is to look to new therapeutic agents that can be taken prophylactically to reduce the risk of tumor formation. For cancer cells to grow and invade, a higher (more alkaline) intracellular pH must occur. We chose to examine a specific nutraceutical agent, which is Vitamin C. The acute effect of Vitamin C exposure on normal colonic crypts has been studied, providing some insight into how Vitamin C achieve its effect. Methods: Distal colon was excised from rats. Following enzymatic digestion single colonic crypts were isolated. Colonic crypts were loaded with pH sensitive dye to measure the intracellular pH changes. Crypts were exposed to solutions +/- Vitamin C. Results: 10 mM Vitamin C decreased Na⁺-dependent intracellular pH recovery. Vitamin C modulates SVCT leading to changes in proton extrusion. Vitamin C entry occurs via either SVCT2 on the basolateral membrane or by transcellular passive diffusion through tight junctions to the apical membrane and then active transport via SVCT1. Conclusion: Acute addition of Vitamin C to the basolateral membrane maintains low intracellular pH for a longer period which could halt and/or prevent tumor formation.

Cell-Surface-Anchored Ratiometric DNA Tweezer for Real-Time Monitoring of Extracellular and Apoplastic pH

“…Extracellular pH, especially the pH in microdomains that occur between cells in tissues, is of great significance in cell physiological and pathological processes . For example, the activities of membrane proteins, including transporters, receptors, enzymes, and ion channels; − tumor growth; inflammation; and neurotrauma, − among others, are pH-related. For plants, the pH of apoplasts (the interphase space between the plasma membrane and the cell wall) affects not only cell-wall structure but also cell elongation and further plant growth. , Hence, development of methods for accurate measurement of extracellular pH is crucial for illustrating its accurate cell functions and better understanding the related cell processes.…”