Disease relevance of Luteoline

• A plant flavone, luteolin, induces expression of Rhizobium meliloti nodulation genes [1].
• In nude mice with xenografted tumors using HAK-1B hepatoma cells, luteolin significantly inhibited the growth of the tumors in a dosage-dependent manner [2].
• In this study, we found that pretreatment with luteolin, a plant flavonoid, greatly sensitized TNFalpha-induced apoptotic cell death in a number of human cancer cell lines; including colorectal cancer COLO205, HCT116 cells and cervical cancer HeLa cells [3].
• Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice [4].
• Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system [5].

High impact information on Luteoline

• Through a random genetic search to find loci that are required for expression of the Rhizobium meliloti nod (nodulation) genes, we isolated a mutant (B4) defective in luteolin-dependent activation of nod gene expression, and found it carries a Tn5 insertion within a chromosomal groEL gene (groELc) located just downstream of a groESc gene [6].
• Luteolin influenced migration by modulating the activity of Rho GTPases, signal transducers involved in transendothelial migration [7].
• Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing monocyte migration across the brain endothelium [7].
• Nodule initiation signals were not involved, since LMW succinoglycan from R. meliloti nodD1D2D3 and nodA mutants and from luteolin-induced wild-type cultures elicited effects similar to LMW succinoglycan from the uninduced wild-type strain [8].
• An overexpression in STAT3 led to resistance to luteolin, suggesting that STAT3 was a critical target of luteolin [2].

Chemical compound and disease context of Luteoline

• Nodulation (nod) genes in Rhizobium meliloti are transcriptionally induced by flavonoid signal molecules, such as luteolin, produced by its symbiotic host plant, alfalfa [9].
• We report here that, although the flavonoids luteolin and quercetin are potent antileishmanial agents, luteolin has great promise for acting as a lead compound in the chemotherapy of leishmaniasis, a major concern in developing countries [10].
• After a 24-h cultivation, the recombinant E. coli produces significant amounts of apigenin (415 microg/l), luteolin (10 microg/l), and genkwanin (208 microg/l) [11].
• The antioxidative effects of luteolin, kaempferol and pinoresinol were further investigated in H4IIE rat hepatoma cells [12].
• Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene [13].

Biological context of Luteoline

• Here we found that pretreatment with a noncytotoxic concentration of luteolin significantly sensitized TRAIL-induced apoptosis in both TRAIL-sensitive (HeLa) and TRAIL-resistant cancer cells (CNE1, HT29, and HepG2) [14].
• Surprisingly, luteolin did not affect VEGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases, a pathway that is considered important for the mitotic effects of VEGF [15].
• In contrast, other flavonoids such as flavone, luteolin, and the structurally similar daidzein arrested the cell cycle at G1 [16].
• Next, we showed that protein kinase C (PKC) activation prevented cell death induced by luteolin and TRAIL via suppression of XIAP down-regulation [14].
• In search of the molecular mechanism responsible for XIAP down-regulation, we found that luteolin and TRAIL promoted XIAP ubiquitination and proteasomal degradation [14].

Anatomical context of Luteoline

• Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3'-kinase activity [15].
• In agreement, luteolin inhibited both VEGF-induced survival and proliferation of human umbilical vein endothelial cells (HUVECs) with an IC(50) of about 5 mumol/L [15].
• The rye-specific luteolin glucuronides decreased uptake rates of E217G and MOC-GS into rye and barley vacuoles to comparable degrees with the mono- and diglucuronidated derivatives (40-60% inhibition) being more effective than the triglucuronide [17].
• Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung [4].
• Inhibition of LPS-stimulated pathways in macrophages by the flavonoid luteolin [18].

Associations of Luteoline with other chemical compounds

• Luteolin is a dietary flavonoid commonly found in some medicinal plants [14].
• Moreover, luteolin inhibited PKC activity, and bisindolylmaleimide I, a general PKC inhibitor, simulated luteolin in sensitizing TRAIL-induced apoptosis [14].
• We investigated the effects of flavonols (kaempferol, quercetin, and myricetin) and flavones (flavone, chrysin, apigenin, luteolin, baicalein, and baicalin) on the tumor necrosis factor-alpha (TNF-alpha)-stimulated ICAM-1 expression [19].
• Additional experiments suggested that apigenin and luteolin were actively inhibiting the IkappaB kinase (IKK) activity, the IkappaBalpha degradation, the nuclear factor-kappaB (NF-kappaB) DNA-protein binding, and the NF-kappaB luciferase activity [19].
• Lipid peroxidation was reduced (UW alone, 2.7 +/- 1.2 vs. UW+quercetin 0.5 +/- 0.2 nmol/mg protein, P < 0.01), and l-threonine uptake completely sustained by pretreatment with quercetin, kaempferol, luteolin, and fisetin [20].

Gene context of Luteoline

• Furthermore, luteolin inhibited vascular endothelial growth factor (VEGF)-induced in vivo angiogenesis in the rabbit corneal assay [15].
• The expression level of Ser(727)-phosphorylated STAT3 was gradually decreased by the luteolin treatment, followed by a fast and clear down-regulation in the active forms of CDK5, which can phosphorylate STAT3 at Ser(727) [2].
• In addition, inhibition of NF-kappaB by luteolin led to augmentation and prolongation of c-Jun N-terminal kinase (JNK) activation induced by TNFalpha [3].
• Immunoblotting of the extracts of tumor tissues showed that luteolin inhibited IGF-1R/AKT signaling [21].
• Overexpression of K179M Akt did not alter LPS-induced TNF-alpha release, suggesting that inhibition of this kinase does not mediate the inhibitory action of luteolin [18].

Analytical, diagnostic and therapeutic context of Luteoline

• Oral administration of luteolin also significantly reduced clinical symptoms [7].
• Direct interaction between luteolin and DNA does not affect the assembly of the enzyme-DNA complex, as evident from the electrophoretic mobility-shift assays [22].
• Extractable proteins from Sinorhizobium meliloti strains AK631 and EK698 (a Tn5-induced noIR-deficient mutant of AK631), grown in tryptone agar (TA) medium with or without the addition of the plant signal luteolin, were separated by two-dimensional gel electrophoresis and compared [23].
• HPLC analysis also allowed us to demonstrate the presence of free luteolin and its monoglucuronide in human serum after ingestion of luteolin [24].
• In addition, flow cytometry analysis of DNA content revealed blocking of the PDGF-BB-inducible cell cycle progression by luteolin [25].

References