Disease relevance of C11924

• In H9 T lymphoma cells, exposure to perillic acid resulted in a dose-dependent depletion of membrane-bound Ras proteins [1].
• The latter strain, and a recombinant Escherichia coli strain that carried the genes of the cym pathway of P. putida Fl, also converted limonene to perillic acid [2].
• To establish the molecular mechanisms of POH and its major metabolite perillic acid (PA) as anti-proliferative agents, their effects on cell proliferation, cell cycle and cell cycle regulatory proteins were studied in HCT 116 human colon cancer cells [3].
• These results indicate that limonene and perillic acid could inhibit the metastatic progression of B16F-10 melanoma cells in mice [4].

High impact information on C11924

• To further assess the role of protein prenylation, VSMCs were exposed to the prenyl transferase inhibitors perillic acid and manumycin A [5].
• Perillic acid and alpha-hydoxyfarnesylphosphonic acid, isoprenylation inhibitors, induced apoptosis of the cells [6].
• However, unlike compactin, the perillic acid-induced effects on lymphocyte proliferation were not prevented by addition of mevalonate [7].
• The role of altered ras oncoprotein (Ras) farnesylation and membrane association in the growth inhibitory effects of several monoterpenes (limonene, perillic acid, perillyl alcohol, menthol, pinene and cineole) was investigated in rat liver epithelial cells [8].
• While POH was not detected in plasma, perillic acid (PA) and dihydroperillic acid (DHPA) were detected in plasma, and the peak levels at 2000 mg/m(2) per dose were approximately 600 micro M (PA) and 50 micro M (DHPA) [9].

Biological context of C11924

• In the present study, perillic acid was found to inhibit cell growth in a dose-dependent manner [10].
• Growth inhibition induced by perillyl alcohol and perillic acid was associated with a fall in the proportion of cells in the S phase and an accumulation of cells in the G1 phase of the cell cycle [11].
• This method was found suitable for quantifying drug concentrations in the range of 0.25 to 200.0 micrograms/ml using a 0.05-ml plasma sample, and was used to study the plasma pharmacokinetics of perillic acid in mice [12].
• Perillyl alcohol and perillic acid were the main products of limonene biotransformation [13].

Anatomical context of C11924

• Effect of S(-) perillic acid on protein prenylation and arterial smooth muscle cell proliferation [14].
• Perillic acid inhibits Ras/MAP kinase-driven IL-2 production in human T lymphocytes [1].
• Administration of various monoterpenes such as carvone (100 micromoles/Kg body wt/dose/animal), limonene (100 micromoles/Kg body wt/dose/animal) and perillic acid (50 micromoles/Kg body wt/dose/animal) were found to increase the total white blood cells (WBC) count in Balb/c mice [15].

Associations of C11924 with other chemical compounds

• Thus, perillic acid and dihydroperillic acid, the two major circulating metabolites of limonene in the rat, are more potent inhibitors of protein isoprenylation than is limonene, and perillic acid is also a more potent inhibitor of cell growth [10].
• It was concluded that perillic acid causes cataract in this system by a mechanism different from lovastatin and that inhibition of isoprenylation is unlikely to be a primary factor in the perillic acid cataract [16].

Gene context of C11924

• In perillic acid-treated cells, the levels of phosphorylated but not total MAPK were also decreased in a dose-dependent manner [1].
• The effects of perillic acid on cytokine secretion were selective: IL-6 and transforming growth factor-beta 1 (TGF-beta 1) generation were unchanged [1].
• Unlike hydroxymethyl-glutaryl-CoA reductase or protein farnesyltransferase inhibitors, perillic acid did not induce a shift of membrane-bound into cytosolic p21ras but depleted total cellular Ras proteins [1].

Analytical, diagnostic and therapeutic context of C11924

• To test that hypothesis we have investigated the effects of perillic acid, an agent reported to inhibit isoprenylation, on rat lenses in organ culture [16].
• Analysis of perillic acid in plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection [12].

References