Cytotoxic Effect of Lipophilic Substitution at 2-, 6-, and 2,6-Positions in Ascorbic Acid and Expression of Matrix Metalloproteinases in Hep G2 Cells, Melanoma Cells and Normal Human Dermal Fibroblast

M.W. Roomi, S. Netke, V. Ivanov, A. Niedzwiecki and M. Rath

Presented at: American College of Nutrition, 42nd Annual Meeting, Orlando, Florida, Oct. 3-7, 2001.

Published in: J. Am. Coll. Nutr. 20: 43, 2001

Abstract

In recent years there has been great interest in the therapeutic implication of ascorbic acid (AA) and its derivatives as anticancer agents. AA had several reactive hydroxy groups, especially at 2- and 6- positions. Both hydrophilic and hydrophobic derivatives were found to be cytotoxic to a number of malignant and nonmalignant cells. In this study we investigated comparative effects of lipophilic substitution at 2- and 6- positions of ascorbic acid on cytotoxicity and expression of some matrix metalloproteinases (MMPs) by two cancer cell lines [melanoma cell A 2058 and HepG2] and normal human dermal fibroblasts (NMDF) in cell culture studies. Ascorbic acid was not toxic to any of these cells even at high concentrations. 2-OctadecylAA was toxic to melanoma cells and the toxicity increased with increased concentration. In the case of HepG2 cells, progressive toxicity was seen only for 2-OctadecyAA and 6-dipalmitoylAA within the range of 100 to 1000uM. 2-OctadecyAA and 6-dipalmitoylAA appeared to be equally toxic to melanoma cells at higher concentrations. 2, 6-DipalmitoylAA for melanoma cells and 2-octadecylAA for HepG2 cells were toxic only at highest concentration. The differences in activity are provably due to their different hydrolysis mechanism and rate. The effect of expression of MMPs by all three cell lines was similar to those on cytotoxicity. The findings indicate that these compounds have the potential as therapeutic agents in the treatment of cancer.

Comment:
Ascorbic acid and its derivatives have been shown to be cytotoxic and inhibit the growth of a number of malignant and non-malignant cell lines in culture and in animal models. In this study, ascorbic acid, which is water-soluble, was not toxic to the melanoma and liver cancer lines tested; however, the lipophilic (lipid soluble) derivatives studied were found to be markedly toxic to these cell lines. This implies that these lipid soluble derivatives, which can cross cell membranes and the blood brain barrier, have therapeutic potential in the treatment of cancer.

Sitemap