In this study, we investigated the intestinal absorption of luteolin and luteolin 7-O-L L-glucoside in rats by HPLC. The absorption analysis using rat everted small intestine demonstrated that luteolin was converted to glucuronides during passing through the intestinal mucosa and that luteolin 7-O-L L-glucoside was absorbed after hydrolysis to luteolin. Free luteolin, its conjugates and methylated conjugates were present in rat plasma after dosing. This suggests that some luteolin can escape the intestinal conjugation and the hepatic sulfation/methylation. LC/ MS analysis showed that the main conjugate which circulates in the blood was a monoglucuronide of the unchanged aglycone. Luteolin in propyleneglycol was absorbed more rapidly than that in 0.5% carboxymethyl cellulose. The plasma concentration of luteolin and its conjugates reached the highest level 15 min and 30 min after dosing with luteolin in propyleneglycol, respectively. HPLC analysis also allowed us to demonstrate the presence of free luteolin and its monoglucuronide in human serum after ingestion of luteolin.z 1998 Federation of European Biochemical Societies.

A perilla seed (Perilla frutescens Britton var. japonica Hara) extract was examined for its antimicrobial activity against oral cariogenic streptococci and periodontopathic Porphyromonas gingivalis. Luteolin, one of the components of perilla seed, showed the strongest antimicrobial effect among the phenolic compounds. According to our results, perilla seed may be the source of an antimicrobial agent that could prevent dental caries and periodontal diseases.

BackgroundEzrin is a member of the ezrin, radixin, and moesin family that provides a functional link between the plasma membrane and the cortical actin cytoskeleton. A correlation between ezrin overexpression and aggressive cancer behavior has been recently reported in various tumor types. However, its roles in the mechanisms underlying progression of tongue squamous cell carcinoma (SCC) are unclear.MethodWe used human tongue SCC and noncancerous tissue microarrays to immunohistochemically analyze the ezrin expression level and its relationship with proliferative activity. The human tongue SCC cell line HSC-3 was used to determine the effects of ezrin RNA interference (RNAi) on cancer cells during MTT; wound healing and invasion assays; immunofluorescence of the actin cytoskeleton; and western blotting of E-cadherin, N-cadherin, β-catenin, and the active and total RhoA/Rac1/cdc42.ResultsEzrin was overexpressed in 46.4% of the tumors examined in human tongue SCC tissue microarrays. Ezrin expression was correlated with the Ki-67 index. Ezrin depletion by RNAi in the HSC-3 cells significantly reduced cell proliferation, migration, and invasiveness and disturbed actin reorganization during podia formation. Its effects on RhoA/Rac1/cdc42 expression were not significant, whereas it enhanced E-cadherin and β-catenin expression and decreased N-cadherin expression.ConclusionsEzrin is often overexpressed in primary tongue SCCs and may have an important role in their growth, migration, and invasiveness possibly via its relationship with the E-cadherin/β-catenin complex and the cadherin switch. Thus, ezrin could be a therapeutic target in tongue SCC.

FXYD3 was originally identified as one of the gene products (mRNAs) highly expressed in murine mammary tumors induced by the transgenic neu or ras but not induced by myc or int-2 oncogenes.1) In human, FXYD3 mRNA was overexpressed in breast cancer cell lines and primary breast cancers, 2) and also in prostate and pancreatic cancers. [3][4][5] Suppression of FXYD3 expression by the small interfering RNA (siRNA) or antisense transfection caused a significant decrease in cellular proliferation of prostate and pancreatic cancer cell lines, respectively. 4,5) Therefore, FXYD3 is involved in proliferation, and is expected to be a tumor marker.FXYD3 is a member of the "FXYD" family proteins, which consist of seven members of small proteins that have a single transmembrane segment, and share a signature sequence of four amino acids "FXYD" (Phe-Xaa-Tyr-Asp) located in the ectodomain close to the transmembrane segment.6) Among the seven members of FXYD proteins, only FXYD2 (Na ϩ ,K ϩ -ATPase g-subunit) and FXYD3 have two isoforms which encode two proteins of different amino acid sequences, respectively. The FXYD3 short-form (FXYD3a) mRNA has an in-frame deletion of 78 nucleotides in the coding sequence compared to the FXYD3 long-form (FXYD3b) mRNA. As a result, the FXYD3b protein has 26 more amino acids in the cytoplasmic domain compared to the FXYD3a protein ( Fig. 1). FXYD family proteins perform fine tuning of ion transport by associating with and modulating the activity of Na ϩ ,K ϩ -ATPase molecule and modifying the activity of ion channels.2,7) FXYD3a slightly decreased the apparent affinity both for intracellular Na ϩ (up to 40%) and extracellular K ϩ (15 to 40%) of Na ϩ ,K ϩ -ATPase whereas FXYD3b slightly increased the apparent affinity for intracellular Na ϩ (about 15%) and decreased the apparent affinity for extracellular K ϩ (up to 50%). 8,9) Both FXYD3 isoforms induced a hyperpolarization-activated chloride current in Xenopus oocytes.2,9) However, physiological roles of FXYD3 isoforms have not been fully understood yet. The expression pattern of FXYD3a and FXYD3b mRNAs has not been cleared. Moreover, it remains to be clear whether the FXYD3 proteins are overexpressed in breast cancers or not. Here, we quantified FXYD3a and FXYD3b mRNAs in human normal tissues and many human cancer cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). We prepared two kinds of antibodies against human FXYD3 protein (one antibody against both FXYD3a and 3b; the other against FXYD3b) and examined the expression pattern of FXYD3 proteins in human cancer cell lines and human breast tissues. We also suppressed the expression of FXYD3 proteins by the treatment of siRNA to study the role of FXYD3 on cellular proliferation of a breast cancer cell line, MCF-7. FXYD3, also known as Mat-8 (Mammary tumor 8 kDa), is one of mRNAs highly expressed in mouse and human breast cancers. Here, we newly found that FXYD3 protein was also overexpressed in human breast cancer specimens; invasive ductal carcinomas and intr...

The effects of phenolic compounds isolated from defatted perilla (Perilla frutescens var. japonica Hara) seed on arachidonate 12-lipoxygenase (12-LO) and 5-lipoxygenase (5-LO) activities were investigated using rat platelets and polymorphonuclear leukocytes. The ethyl acetate layer obtained by partitioning the ethanolic extract of defatted perilla seed proved to have significant inhibitory activity against lipoxygenases. Potent inhibitory principles in the ethyl acetate layer were isolated and identified as luteolin, chrysoeriol, and rosemarinic acid and its methyl ester. The most effective inhibitor of lipoxygenases was luteolin (IC50 = 20 and 102 nM for 12-LO and 5-LO, respectively). These results indicate that defatted perilla seed, now an industrial waste product, may be developed into a useful source of an agent that prevents allergic hyper-reactivity and inflammatory responses due to its antilipoxygenase activity. Keywords: Arachidonic acid; lipoxygenase; perilla seed; luteolin