Positive Health Online

Abstract

ROOMI and colleagues, Linus Pauling Institute, Oregon State University, Corvallis 97331 USA write that in recent years L-ascorbic acid (AA) and its isomers have raised considerable interest as anticancer agents, although the mechanism has remained unknown.

Background

Methodology

The authors write that AA isomers are almost identical in their physical and chemical properties, but they differ widely in their biological properties. AA, a lactone sugar has a number of reactive positions, especially at 2- and 6-. There are a number of studies regarding the cytotoxic effect of AA and its isomers on malignant and nonmalignant cell lines; however, no work has been reported on the comparative effects of substitutions at these active sites. In this study, the authors investigated the comparative cytotoxicity of substitutions on the malignant leukaemia P388 cell line in culture. Results: All 2-substituted and the 2,6-substituted AA derivatives tested were found to be nontoxic and ineffective in preventing cell growth. In contrast, all 6-substituted AA derivatives were highly toxic at all levels, even at the lowest concentrations (1 microg/ml).

Results

Conclusion

These results suggest that substitution at 2-, 6- and 2,6-positions in AA have a varying effect upon toxicity. The 2-, and 2,6-substituted AA derivatives are stable compounds, resistant to hydrolysis which render them inactive. The cytotoxicity of the 6-substituted derivatives may be explained by one of the following mechanisms, which need to be explored: 1) the hydrolysis rate may differ; or 2) the chemical structure itself may affect toxicity. Further studies are in progress to understand the mechanism.

References

Roomi MW et al. Cytotoxic effect of substitution at 2-, 6-, and 2,6-positions in ascorbic acid on malignant cell line. Cancer Biochem Biophy 16(4): 295-300. Nov 1998.