Structure and activity relationship of monogalactosyl diacylglycerols, which selectively inhibited in vitro mammalian replicative DNA polymerase activity and human cancer cell growth.
The glycoglycerolipid, monogalactosyl diacylglycerol (MGDG), containing two alpha-linolenic acids (C18:3), was isolated from bitter melon as a potent and selective inhibitor of mammalian DNA polymerase (pol) species such as pols alpha, gamma, delta, and epsilon with IC(50) values of 17.6-37.2muM. This MGDG also suppressed the growth of six human cancer cell lines, although normal human cell lines were not affected. This compound (i.e., MGDG-C18:3-C18:3) was a stronger inhibitor than both MGDG-C18:1-C18:0 and MGDG-C18:0-C18:0. In this study, we discussed the structure-function relationship in the selective inhibition of mammalian replicative pols and human cancer cell proliferation by MGDGs.
Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan.
Yuki
Y
Matsui
Takahiko
T
Hada
Naoki
N
Maeda
Yoshihiro
Y
Sato
Yasuhiro
Y
Yamaguchi
Toshifumi
T
Takeuchi
Masaharu
M
Takemura
Fumio
F
Sugawara
Kengo
K
Sakaguchi
Hiromi
H
Yoshida
Yoshiyuki
Y
Mizushina
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D019662:Cucurbitaceae / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D038983:Galactolipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D038983:Galactolipids; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts; C009909:monogalactosyldiacylglycerol; D004259:DNA-Directed DNA Polymerase