aurapten and Neoplasms

O-Prenyl secondary metabolites (3,3-dimethylallyl, geranyl-, farnesyl- and related biosynthetic derivatives) represent a class of rarely occurring natural products. In the last two decades such compounds have been found to exert promising and effective pharmacological activities, mainly in terms of anti-cancer properties. To date about 350 oxyprenylated secondary metabolites, the most part of which having a phenylpropanoid or a polyketide core, have been extracted from plants mainly belonging to the Rutaceae, Apiaceae, and Fabaceae families, and from fungi and bacteria. The aim of this comprehensive review is to make a survey of the in so far reported literature citations about O-prenyl secondary metabolites exhibiting in vitro and in vivo anti-cancer properties from phytochemical and pharmacological point of views.

Topics: Biological Products; Cell Proliferation; Chalcones; Coumarins; Fungi; Humans; Molecular Structure; Neoplasms; Oxidation-Reduction; Plant Extracts; Prenylation

In the present study, we explored the suppressive activities of 1'-acetoxychavicol acetate (ACA), auraptene, nobiletin, and zerumbone toward LPS-induced cyclooxygenase (COX)-2 mRNA expression in mouse macrophages and the underlying molecular mechanisms. Pretreatment of RAW264.7 cells with LPS led to the activation of mitogen-activated protein kinase (MAPK)s [p38, extracellular signal-regulated kinase (ERK)1/2, c-Jun NH2-terminal kinase (JNK)1/2] and Akt, together with degradation of the inhibitor of nuclear factor-kappaB (IkappaB)-alpha protein and nuclear translocation of nuclear factor (NF)-kappaB p65, and the resultant activation of activator protein (AP)-1, NF-kappaB, and cAMP-responsive element-binding protein (CREB) transcription factors. ACA abrogated ERK1/2 and JNK1/2, but not p38 MAPK, as well as the activation of those transcription factors. Although it allowed LPS-triggered phosphorylation of those MAPKs and NF-kappaB nuclear translocation, nobiletin suppressed the activation of AP-1, NF-kappaB, and CREB. Zerumbone had no effect on those transcription factors, though it attenuated COX-2 mRNA expression, suggesting that it disrupts the stabilization of COX-2 mRNA. Conversely, zerumbone significantly accelerated spontaneous COX-2 mRNA decay, the potency of which was comparable with that of SB203580, an inhibitor of p38 MAPK, whose activation has key roles in the proinflammatory mRNA stabilization processes. Because SB203580 but not zerumbone suppressed LPS-induced p38 MAPK activation, the molecular targets of zerumbone may be MAPK-activated protein kinase-2 or located downstream. However, auraptene suppressed the expression of COX-2 protein but not mRNA, implying that it targets translation. We propose that these phytochemicals are promising chemopreventive agents for inflammation-associated carcinogenesis. Their use in combination may enhance their efficacy because of their different modes of action.

Topics: Animals; Benzyl Alcohols; Coumarins; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Flavones; Lipopolysaccharides; Macrophages; Mice; Mitogen-Activated Protein Kinases; Neoplasms; RNA, Messenger; Sesquiterpenes; Terpenes