Inhibitory Effect on Replicative DNA Polymerases, Human Cancer Cell Proliferation, and In Vivo Anti-Tumor Activity by Glycolipids from Spinach

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Abstract:

We succeeded in purifying a major glycolipids fraction (i.e., Fraction-II) in the class of monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG) from spinach using hydrophobic column chromatography. Fraction-II inhibited the activities of replicative DNA polymerases (pols) such as α, δ and η, and mitochondrial pol g with IC50 values of 43 - 79 μg/ml, but had no influence on the activity of repair-related pols β and lλ. MGDG, DGDG, SQDG were purified from Fraction-II of spinach using silica gel column chromatography, and SQDG was the strongest inhibitor of mammalian pols in the three glycolipids. Therefore, SQDG and its related compounds were chemically synthesized, and the sulfate group and fatty acid moiety of the compound were suggested to be important for pol inhibition. These glycolipids showed no effect even on the activities of plant pols, prokaryotic pols and other DNA metabolic enzymes such as T4 polynucleotide kinase, T7 RNA polymerase and deoxyribonuclease I. Fraction-II also inhibited the proliferation of human cervix carcinoma (HeLa) cells with LD50 values of 57 μg/ml, and could halt the cell cycle at the G1-phase, and subsequently induced severe apoptosis. In an in vivo anti-tumor assay on nude mice bearing solid tumors of HeLa cells, Fraction-II was shown to be a promising suppressor of solid tumors. Histopathological examination revealed that tumor necrosis with hemorrhage was significantly enhanced with Fraction-II in vivo. The spinach Fraction-II containing SQDG might be a potent anti-tumor compound, and may be a healthy food substance with antitumor activity.

Keywords: DNA polymerase; Glycolipids; anti-tumor activity; digalactosyl diacylglycerol (DGDG); inhibitor; monogalactosyl diacylglycerol (MGDG); spinach; sulfoquinovosyl diacylglycerol (SQDG)

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707780362952

Affiliations: Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, 518 Arise, Ikawadanicho, Nishi-ku, Kobe, Hyogo 651-2180,Japan.

Publication date: April 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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