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A Galactolipid Possesses Novel Cancer Chemopreventive Effects by Suppressing Inflammatory Mediators and Mouse B16 Melanoma

¹ Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, Republic of China and ² Department of Forestry, National Chung-Hsing University, Taichung, Taiwan, Republic of China

Requests for reprints: Lie-Fen Shyur, Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, Republic of China. Phone: 886-2-26515028; Fax: 886-2-26515028; E-mail: lfshyur{at}ccvax.sinica.edu.tw.

Crassocephalum rabens (Asteraceae) is a popular anti-inflammatory folk medicine and food supplement. We investigated the cancer chemopreventive bioactivity of C. rabens phytocompounds in vitro and in vivo using cell- and gene-based bioassays and a mouse B16 melanoma model. The bioactive glyceroglycolipid 1,2-di-O--linolenoyl-3-O-ß-galactopyranosyl-sn-glycerol (dLGG) that was identified from C. rabens was found in vitro and in vivo to be a potent nitric oxide (NO) scavenger. dLGG treatment inhibited both mRNA and protein expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in murine macrophages and inhibited COX-2 gene transcription in 12-O-tetradecanoylphorbol-13-acetate (TPA)–treated B16 cells. In immunohistochemical studies, dLGG inhibited TPA-induced expression of COX-2 and nitration of proteins in mouse skin. dLGG could also significantly inhibit lipopolysaccharide-induced prostaglandin E₂ production in murine macrophages. Furthermore, dLGG prevented nuclear translocation of cytoplasmic nuclear factor-B (NF-B) by suppressing IB phosphorylation and degradation. Structure-activity relationship study by electrophoretic mobility shift assay indicated that the dilinolenoylglycerol moiety in dLGG is the essential structural feature preventing NF-B·DNA complex formation. A dLGG-enriched extract from C. rabens (10 mg/kg) markedly suppressed B16 melanoma growth in C57BL/6J mice following i.p. administration, an effect comparable with that of cisplatin, a cancer chemotherapeutic drug. This study shows the detailed molecular mechanism(s) underlying the anti-inflammatory and tumor-suppressive effects of a natural galactolipid. [Cancer Res 2007;67(14):6907–15]