A novel DNA polymerase inhibitor and a potent apoptosis inducer: 2-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride with stearic acid.
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.
Murakami
Chikako
C
Department of Nutritional Science, Laboratory of Food & Nutritional Sciences, Kobe-Gakuin University, Nishi-ku, Hyogo 651-2180, Kobe, Japan.
Yamazaki
Takayuki
T
Hanashima
Shinya
S
Takahashi
Shunya
S
Takemura
Masaharu
M
Yoshida
Shonen
S
Ohta
Keisuke
K
Yoshida
Hiromi
H
Sugawara
Fumio
F
Sakaguchi
Kengo
K
Mizushina
Yoshiyuki
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002463:Cell Membrane Permeability; D019927:Cyclin E / Q000032:analysis; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008049:Lipase; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors; D013229:Stearic Acids / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C471841:2-stearoyl-3-O-sulfoquinovosylglyceride; D000970:Antineoplastic Agents; D019927:Cyclin E; D004791:Enzyme Inhibitors; D006017:Glycolipids; D019384:Nucleic Acid Synthesis Inhibitors; D013229:Stearic Acids; D016159:Tumor Suppressor Protein p53; C031183:stearic acid; D004256:DNA Polymerase I; D008049:Lipase