Disease relevance of Orobol

• Differential sensitization by orobol in proliferating and quiescent human ovarian carcinoma cells [1].
• To determine whether prevalence and intensity of infection are factors in morbidity in schistosomiasis japonica, a cross-sectional study was undertaken in three villages in Leyte, Philippines, namely, Santol (A), Santa Rosa (B), and Macanip (C) [2].

High impact information on Orobol

• The intracellular genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone mediates G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling pathway [3].
• Experiments using isolated DNA revealed a metal-dependent mechanism of oxidative DNA damage induced by orobol and 7,3',4'-OH-IF [4].
• It inhibited phosphatidylinositol turnover with an IC50 of about 1 microgram/ml; thus, its inhibitory activity was 6-times stronger than that of genistein or orobol [5].
• In addition, the isolated constituents, erycibenin A (1, IC50 = 79 microM), genistein (6, 29 microM), orobol (7, 36 microM), and 5,7,4'-trihydroxy-3'-methoxyisoflavone (8, 55 microM) exhibited inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes [6].
• CONCLUSIONS: These results indicate that orobol produced DDP sensitivity in human ovarian carcinoma cells by inducing apoptosis through the MT-dependent signaling pathway [7].

Anatomical context of Orobol

• Since sensitivity to rhodamin 123 is indicative of mitochondrial membrane potential, these results imply that mitochondrial alterations may be an important component of the orobol sensitization effect in these cells [1].
• Confocal laser microscopy of cells stained with the mitochondria (MT)-specific dye Rh revealed that orobol decreased Rh-fluorescent intensity [7].
• These compounds also inhibited endothelial cell proliferation, with orobol causing the greatest inhibition at lower concentrations [8].

Associations of Orobol with other chemical compounds

• In the order of IC50 values the inhibitory potency in the IL-5 bioassay was sophoricoside > orobol (9.8 microM) approximately equal to genistin (10.6 microM) > genistein (51.9 microM) [9].
• The caspase-3-inhibiting peptide Ac-DEVD-CHO completely inhibited the orobol sensitization effect but did not block DDP cell cytotoxicity per se [7].
• Because orobol had no effect on conventional mechanisms such as DDP accumulation or cellular metallothionein and glutathione content, we have focused on the apoptotic signaling pathway [7].
• Orobol induced a significant increase in apoptosis in DDP-treated cells, as estimated by frequency of condensed nuclear chromatin with Hoechst 33342 stain, although orobol alone did not have any effect on apoptotic potential [7].

Gene context of Orobol

• Orobol which showed no or only slight inhibition of tyrosine hydroxylase and dopamine beta-hydroxylase exhibited a significant hypotensive effect on spontaneously hypertensive rats [10].
• Orobol was the only metabolite formed after incubation with CYP1A2 [11].
• Clonogenic survival assay was used to determine the effect of orobol, a potent PI4-kinase inhibitor, on DDP sensitivity in human ovarian carcinoma 2008 cells [1].
• METHODS AND RESULTS: Orobol produced >2-fold DDP sensitivity in human ovarian carcinoma 2008 cells and its DDP-resistant variant 2008/C13*5.25 cells (C13) [7].
• When the expression was examined in the presence of various agents modulating intracellular signals, isoflavonoids (genistein, psi-tectorigenin, and orobol) significantly decreased c-myc mRNA levels, in a dose dependent manner [12].

Analytical, diagnostic and therapeutic context of Orobol

• Electron microscopy of these cells showed that orobol induced swelling and condensation of MT [7].

References