A galactolipid possesses novel cancer chemopreventive effects by suppressing inflammatory mediators and mouse B16 melanoma.

Abstract

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.

• Authors: Chia-Chung Hou, Yi-Ping Chen, Jyh-Horng Wu, Chi-Chang Huang, Sheng-Yang Wang, Ning-Sun Yang, Lie-Fen Shyur
• Journal: Cancer research (Cancer Res) Vol. 67 Issue 14 Pg. 6907-15 (Jul 15 2007) ISSN: 0008-5472 [Print] United States
• PMID: 17638902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Galactolipids
• Plant Extracts
• I-kappa B Kinase

Topics

• Active Transport, Cell Nucleus
• Animals
• Anticarcinogenic Agents (pharmacology)
• Asteraceae (metabolism)
• Cell Survival
• Female
• Galactolipids (chemistry)
• I-kappa B Kinase (metabolism)
• Immunohistochemistry
• Inhibitory Concentration 50
• Macrophages (metabolism)
• Melanoma, Experimental
• Mice
• Mice, Inbred C57BL
• Plant Extracts (metabolism)