Anti-Tumor Effects of the Glycolipids Fraction from Spinach which Inhibited DNA Polymerase Activity

Abstract:

We succeeded in purifying the fraction of monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), and sulfoquinovosyl diacylglycerol (SQDG) containing the major glycolipids from a green vegetable, spinach (Spinacia oleracea L.). This glycolipids fraction inhibited the activities of replicative DNA polymerases (pols) such as α, δ, and ε, and mitochondrial pol γ with IC₅₀ values of 44.0–46.2 μg/ml, but had no influence on the activity of repair-related pol β. The fraction also inhibited the proliferation of human cervix carcinoma (HeLa) cells with LD₅₀ values of 57.2 μg/ml. In an in vivo anti-tumor assay on nude mice bearing solid tumors of HeLa cells, the fraction was shown to be a promising suppressor of solid tumors. Histopathological examination revealed that tumor necrosis with hemorrhage was significantly enhanced with the glycolipids fraction in vivo. The spinach glycolipids fraction might be a potent anti-tumor compound, and this fraction may be a healthy food substance with anti-tumor activity.

Acknowledgments and Notes

We are grateful to Dr. Masaharu Takemura of Tokyo University of Science (Tokyo, Japan), Dr. Akio Matsukage of Japan Women's University (Tokyo, Japan) and Dr. Kengo Sakaguchi of Tokyo University of Science (Chiba, Japan) for preparing calf pol α, rat pol β, and human pols δ and ε, respectively, and for valuable discussions concerning inhibitors. This work was supported in part by a Grant-in-aid for Kobe-Gakuin University Joint Research (A) (H. Y. and Y. M.) and “Cooperative Research Center of Life Sciences” Project for Private Universities: matching fund subsidy from MEXT (Ministry of Education, Culture, Sports, Science and Technology), 2006–2010 (H. Y. and Y. M.). Y. M. acknowledges Grants-in-aid from the Mochida Memorial Foundation for Medical and Pharmaceutical Research (Japan), and the Nakashima Foundation (Japan).