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.
Published in: Journal of the American College for Nutrition 20:
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
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.
findings indicate that these compounds have the potential as therapeutic
agents in the treatment of cancer.