Metastatic and Cytotoxic Effects of Ascorbigen and iso-Ascorbigen in Human Cancer Cell Lines.
M.W. Roomi, A. Bogale, V. Ivanov, S. Netke, A. Niedzwiecki and M. Rath
Presented at: American College of Nutrition, 43rd Annual Meeting,
San Antonio, Texas, Oct 3-6, 2002.
Diets rich in cruciferous vegetables such as cabbage, broccoli and Brussels sprout have been shown to prevent certain types of cancer. This discovery led to the isolation of ascorbigen (Ascorb) in cabbage as a major indole-containing compound—a structure fusing indole 3-carbinol (I3C) with ascorbic acid (AA). Iso-ascorbigen (iso-Ascorb) is a synthetic analogue in which AA is replaced by iso-ascorbic acid (iso-AA). Very little is known about the effect of these two compounds as antineoplastic agents.
In the present study, we examined the metastatic, antiproliferative and cytotoxic activities of Ascorb and iso-Ascorb in human skin cancer (Melanoma), liver cancer (HepG2) and colon cancer (HCT 116) in vitro. For comparative purposes, AA, iso-AA, and I3C were also used. Cytotoxicity or proliferation was determined by MTT assay, and the metastatic potential of these cancer cell lines was determined by the levels of secretion of matrix metalloproteinases (MMPs). Excessive MMPs activity is associated with malignancy and has been increased in patients suffering from cancer. Ascorb was toxic to melanoma, HepG2 and colon cancer cell lines and its toxicity increased with increasing concentrations from 100 to 1000 mM. Increasing concentration of Ascorb had a significant negative impact on cellular secretion of MMPs.
Comparatively, iso-ascorb was found to be less toxic. AA and iso-AA were not toxic to any of these cell lines at similar concentrations; no change in MMPs was observed. However, I3C was toxic to these cancer cell lines with increasing concentration up to 1000uM. In addition, the MMP secretion decreased with increasing concentration. It is probable that Ascorb and iso-Ascorb are transformed into I3C, AA and iso-AA by these cells, which in turn cause toxicity. These results suggest that Ascorb and iso-Ascorb are toxic to human cancer cells of differing origin.
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