A novel DNA polymerase inhibitor and a potent apoptosis inducer: 2-mono-O-acyl-3-O-(α-D-sulfoquinovosyl)-glyceride with stearic acid

Synthetic Organic Chemistry Laboratory, RIKEN, Вако, Saitama, Japan
Biochimica et Biophysica Acta (Impact Factor: 4.66). 02/2003; 1645(1):72-80. DOI: 10.1016/S1570-9639(02)00521-6
Source: PubMed

ABSTRACT Sulfo-glycolipids in the class of sulfoquinovosyl diacylglycerol (SQDG) including the stereoisomers are potent inhibitors of DNA polymerase alpha and beta. However, since the alpha-configuration of SQDG with two stearic acids (alpha-SQDG-C(18)) can hardly penetrate cells, it has no cytotoxic effect. We tried and succeeded in making a permeable form, sulfoquinovosyl monoacylglycerol with a stearic acid (alpha-SQMG-C(18)) from alpha-SQDG-C(18) by hydrolysis with a pancreatic lipase. alpha-SQMG-C(18) inhibited DNA polymerase activity and was found to be a potent inhibitor of the growth of NUGC-3 cancer cells. alpha-SQMG-C(18) arrested the cell cycle at the G1 phase, and subsequently induced severe apoptosis. The arrest was correlated with an increased expression of p53 and cyclin E, indicating that alpha-SQMG-C(18) induced cell death through a p53-dependent apoptotic pathway.

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    • "Also, 3 -SO 3 -␤-d-GalAAG may be responsible for the binding of the HIV glycoprotein 120 to spermatozoa and subsequent transmission of HIV to the sexual partner (Brogi et al., 1998 and references therein). Studies of the plant glycolipids have shown that both the nonionic galactolipids and the sulfonoquinovosyldiacylglycerol are potent inhibitors of both eukaryotic DNA polymerases and the HIV reverse transcriptase (Lau et al., 1993; Loya et al., 1998; Mizushina et al., 2003; Murakami et al., 2003; Mannock and McElhaney, 2004, and references therein). In addition, both ionic and nonionic glycolipids have been shown to be potent inhibitors of tumour growth in a variety of cancers (Lu et al., 1994; Colombo et al., 2002; Sahara et al., 2002; Ohta et al., 2001; Mannock and McElhaney, 2004, and references therein). "
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