Disease relevance of farnesol

• We have previously shown that, among various isoprenoids, farnesol and geranylgeraniol specifically induced actin fiber disorganization, growth inhibition, and apoptosis in human lung adenocarcinoma A549 cells (Miquel, K., Pradines, A., and Favre, G. (1996) Biochem. Biophys. Res. Commun. 225, 869-876) [1].
• We then gave 500 mg/kg body weight farnesol by gavage to Sabra hypertensive and normotensive rats and found that farnesol reduced blood pressure significantly in the hypertensive strain for at least 48 hours [2].
• Lovastatin's effects on cell viability were partially reversed in the presence of farnesol, and treatment of mesothelioma cells with a specific farnesyl-protein transferase (FTP) inhibitor decreased cell viability and induced morphologic changes indistinguishable from those caused by lovastatin [3].
• The purpose of this study was to determine the role of farnesol during infection with a well-established mouse model of systemic candidiasis with C. albicans A72 administered by tail vein injection [4].
• Effect of Farnesol on Staphylococcus aureus Biofilm Formation and Antimicrobial Susceptibility [5].

High impact information on farnesol

• Farnesol metabolites are generated intracellularly and are required for the synthesis of cholesterol, bile acids, steroids, retinoids, and farnesylated proteins [6].
• It was further demonstrated that AFC and farnesol inhibited KCl and NaF-induced contractions, suggesting a complex action on Ca2+ channels and G protein-dependent pathways [7].
• Using in vitro structural assays, we now show that the pathway derivative farnesol causes Hmg2p to undergo a change to a less folded structure [8].
• Cell division was inhibited by adding either alpha factor or farnesol [9].
• The ability of Nicotiana tabacum cell cultures to utilize farnesol (F-OH) for sterol and sesquiterpene biosynthesis was investigated [10].

Chemical compound and disease context of farnesol

• Nerolidol and farnesol also sensitized Escherichia coli to polymyxin B [11].
• The mevalonate pathway intermediary geranyl-geraniol (GGOH) but not farnesol (FOH) significantly inhibited the anticancer effects of ZOL against osteosarcoma cells [12].
• We then tested the relative in vivo antitumor activities of dietary farnesol, geraniol, and perillyl alcohol against transplanted PC-1 hamster pancreatic adenocarcinomas [13].
• Unlike the bacteriochlorophylls c, d, and e of the Chlorobiaceae, bacteriochlorophyll cs of Chloroflexus is not a mixture of isomeric and homologous molecules; 2. the esterifying alcohol of the propionic acid side chain is neither farnesol nor another isoprenoid alcohol, but is the straight chain aliphatic (C-18) stearylalcohol [14].
• Actions of farnesol and xylitol against Staphylococcus aureus [15].

Biological context of farnesol

• Induction of apoptosis by farnesol (FOH) and other cytotoxic drugs has been shown to alter PtdCho synthesis via the CDP-choline pathway [16].
• Geranylgeraniol and farnesol prevented incadronate-induced apoptosis and had a partial effect on cell cycle arrest [17].
• This superinduction was reversed by geranylgeraniol, but not by farnesol, further confirming that inhibition of geranylgeranylation, not farnesylation, is responsible for enhanced NOS-2 expression [18].
• Farnesol increases resistance to oxidative stress in C. albicans but, interestingly, induces apoptotic-like cell death in Aspergillus nidulans, suggesting that this molecule has multiple and opposing functions [19].
• These data demonstrate the molecular mechanism of geranylgeraniol and farnesol effects and suggest that the mevalonate pathway, leading notably to prenylated proteins, might be linked to the control of cell proliferation through the regulation of phosphatidylcholine biosynthesis [1].

Anatomical context of farnesol

• Altogether, our results indicate that farnesol is an inhibitor of vascular smooth muscle Ca2+ signaling with plasma membrane Ca2+ channel blocker properties [20].
• Farnesol inhibits L-type Ca2+ channels in vascular smooth muscle cells [20].
• A single base pair mutation of the AP-1 site at -2116 to -2110 bp abolished farnesol responsiveness, identical to effects by peroxisome proliferator-activated receptor (PPARalpha) activators [21].
• Farnesol stimulates differentiation in epidermal keratinocytes via PPARalpha [21].
• Inside the hepatocytes, activated farnesol X receptor will decrease further bile acid uptake by reducing the levels of sodium taurocholate co-transporting polypeptide, and stimulating the export of bile acid by increasing the expression of the bile salt export pump [22].

Associations of farnesol with other chemical compounds

• The effect is reversible, biologically relevant by numerous criteria, highly specific for farnesol structure, and requires an intact Hmg2p sterol-sensing domain [8].
• Uncoupling farnesol-induced apoptosis from its inhibition of phosphatidylcholine synthesis [23].
• Further resolution of the material by normal phase liquid chromatography and thin layer chromatography demonstrated the presence of farnesol, nerolidol, and other unidentified hydrophobic derivatives [24].
• Effects of farnesol and JH on INV and transglutaminase mRNA levels were additive with high calcium concentrations (1.2 mM) that independently stimulate keratinocyte differentiation [21].
• Earlier experiments with animal and human arteries have shown that farnesol, a natural 15-carbon (C15) isoprenoid, is an inhibitor of vasoconstriction (Roullet, J.-B., Xue, H., Chapman, J., McDougal, P., Roullet, C. M., and McCarron, D. A. (1996) J. Clin. Invest. 97, 2384-2390) [20].
• Growth with C. albicans leads to decreased production of PQS and pyocyanin by P. aeruginosa, suggesting that the amount of farnesol produced by the fungus is sufficient to impact P. aeruginosa PQS signalling [25].

Gene context of farnesol

• Kinetic analysis and inhibition experiments indicate that, in liver microsomes, UGT1A1 is primarily responsible for farnesol glucuronidation; however, in intestine microsomes, UGT2B7 is probably the major isoform involved, with a very-low-micromolar K(m) [26].
• Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation [27].
• Finally, topical applications of farnesol increased mRNA and protein levels of the differentiation-specific genes, profilaggrin and loricrin, determined by immunohistochemistry and in situ hybridization, in wild-type but not in PPARalpha-/- murine epidermis [21].
• Furthermore, the farnesol X receptor induces the small heterodimer partner, an atypical nuclear receptor, which attenuates bile acid synthesis by inhibiting the action of the orphan nuclear receptor, liver receptor homolog-1, which is a competence factor for CYP7A1 transcription [22].
• Mammalian cells expressing CYP2E1 demonstrated further farnesol metabolism to alpha,omega-prenyl dicarboxylic acids [28].
• The activation of the NF-kappaB pathway by farnesol might be part of a prosurvival response during farnesol-induced ER stress [29].

Analytical, diagnostic and therapeutic context of farnesol

• High pressure liquid chromatography analysis of the cleavage products on a C-18 column showed a major peak of radioactivity that co-eluted with a farnesol standard [30].
• Seven dicarboxylic acids were isolated by high performance liquid chromatography (HPLC) from urine of either rats or dogs treated with zaragozic acid A or rats fed farnesol [31].
• Our findings demonstrate that in vitro, farnesol causes reductase to become detergent insoluble and thus lost from immunoprecipitation experiments, yielding apparent degradation [32].
• We used cDNA microarray analysis to identify the changes in the gene expression profile of a C. albicans biofilm inhibited by farnesol [33].
• Confocal scanning laser microscopy was used to visualize and confirm normal and farnesol-inhibited biofilms [33].

References