A galactolipid possesses novel cancer chemopreventive effects by suppressing inflammatory mediators and mouse B16 melanoma.
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-alpha-linolenoyl-3-O-beta-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 E(2) production in murine macrophages. Furthermore, dLGG prevented nuclear translocation of cytoplasmic nuclear factor-kappaB (NF-kappaB) by suppressing IkappaBalpha 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-kappaB.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.
Hou
Chia-Chung
CC
Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, Republic of China.
Chen
Yi-Ping
YP
Wu
Jyh-Horng
JH
Huang
Chi-Chang
CC
Wang
Sheng-Yang
SY
Yang
Ning-Sun
NS
Shyur
Lie-Fen
LF
D021581:Active Transport, Cell Nucleus; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019659:Asteraceae / Q000378:metabolism; D002470:Cell Survival; D005260:Female; D038983:Galactolipids / Q000737:chemistry*; D051550:I-kappa B Kinase / Q000378:metabolism; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000378:metabolism
D016588:Anticarcinogenic Agents; D038983:Galactolipids; D010936:Plant Extracts; D051550:I-kappa B Kinase