Cytotxic Effect of Lipophlic Substitution at 2-, 6-, and 2,6-Positions in Ascorbic Acid and Expression of Matrix Metalloproteinases in Hep G2 Cells, Melanoma Cells and Norman 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.
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 cytotoxity 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 highest concentration. 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 cytotoxity. The findings indicate that these compounds have the potential as therapeutic agents in the treatment of cancer.
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