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Paranasal sinus tumors are a heterogeneous group of neoplasms (with paranasal schwannomas being a rare subtype) that are often present with non-specific symptoms, such as nasal obstruction and epistaxis. Thus, early diagnosis is crucial for optimal management. This study presents 2 cases of paranasal schwannomas, detailing their clinical presentation, diagnostic methods, and treatment approaches. Both patients underwent endoscopic sinus surgery with successful tumor excision and had no significant complications or recurrences during follow-up. Diagnosis was based on a combination of clinical examination, radiological imaging (computed tomography and magnetic resonance imaging), and histopathological confirmation with immunohistochemical staining. Treatment consisted primarily of endonasal resection, with consideration of frontal craniotomy if necessary. This study aims to contribute to the understanding of paranasal schwannomas and emphasizes the importance of early detection and treatment to improve patient outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Platinum resistance is a major obstacle to the treatment of ovarian cancer and is correlated with poor clinical outcomes. Intratumor heterogeneity plays a key role in chemoresistance. Recent studies have emphasized the contributions of genetic and epigenetic factors to the development of intratumor heterogeneity. Although the clinical significance of multi-subunit chromatin remodeler, switch/sucrose nonfermenting (SWI/SNF) complexes in cancers has been reported, the impacts of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4/subfamily A, member 2 (SMARCA4/A2) expression patterns in human cancer tissues have not been fully elucidated. Here, we show that low expression of SMARCA4 and high expression of SMARCA2 are associated with platinum resistance in ovarian high-grade serous carcinoma (HGSC) cells. We used fluorescence multiplex immunohistochemistry (fmIHC) to study resected specimens; we examined heterogeneity in human HGSC tissues at the single-cell level, which revealed that the proportion of cells with the SMARCA4 low /SMARCA2 high phenotype was positively correlated with clinical platinum-resistant recurrence. We used stable transfection of SMARCA2 and siRNA knockdown of SMARCA4 to generate HGSC cells with the SMARCA4 low /SMARCA2 high phenotype; these cells had the greatest resistance to carboplatin. Bioinformatics analyses revealed that the underlying mechanism involved in substantial alterations to chromatin accessibility and resultant fibroblast growth factor (FGF) signaling activation, MAPK pathway activation, BCL2 overexpression, and reduced carboplatin-induced apoptosis; these were confirmed by in vitro functional experiments. Furthermore, in vivo experiments in an animal model demonstrated that combination therapy with carboplatin and a fibroblast growth factor receptor (FGFR) inhibitor promoted cell death in HGSC xenografts. Taken together, these observations reveal a specific subpopulation of HGSC cells that is associated with clinical chemoresistance, which may lead to the establishment of a histopathological prediction system for carboplatin response. Our findings may facilitate the development of novel therapeutic strategies for platinum-resistant HGSC cells. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

This study aimed to investigate the effect of polymers and storage relative humidity on amorphous rebamipide (RB) and its solid dispersion phase transformation using chemometrics based on multiple datasets. The amorphous RB was prepared using particle mixture and grinding methods with hydroxypropyl cellulose, polyvinylpyrrolidone, and sodium dodecyl sulfate. Prepared amorphous RB and solid dispersion samples were stored under a relative humidity of 30% and 75% for four weeks. Infrared spectra of the dispersion samples suggested that the hydrogen bond network was constructed among quinolinone, carbonyl acid, and amide of RB and other polymers. The dataset combining near-infrared (NIR) spectra and powder X-ray diffractograms were applied to principal component analysis (PCA). The relationship between diffractograms and NIR spectra was evaluated using loadings and the PCA score. The multiple spectra analysis is useful for evaluating model amorphous active pharmaceutical ingredients without a standard sample.

Lung cancer is a common type of cancer that represents a health problem worldwide; lung adenocarcinoma (LUAD) is a major subtype of lung cancer. Although several treatments for LUAD have been developed, the mortality rate remains high because of uncontrollable progression. Further biological and clinicopathological studies are therefore needed. Here, we investigated the role of family with sequence similarity 111 member B (FAM111B), which is highly expressed in papillary-predominant LUAD; however, its role in cancer is unclear. An immunohistochemical analysis confirmed that papillary-predominant adenocarcinomas exhibited higher expression of FAM111B, compared with lepidic-predominant adenocarcinomas. Additionally, FAM111B expression was significantly correlated with clinical progression. In vitro functional analyses using FAM111B-knockout cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of KRAS-driven LUAD under serum-starvation conditions. Furthermore, FAM111B regulated cyclin D1-CDK4-dependent cell cycle progression by degradation of p16. In summary, we revealed the clinical importance of FAM111B in human tumor tissues, as well as its function as a degradative enzyme. Therefore, FAM111B has potential as a clinicopathological prognostic marker for LUAD., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Benexate, a drug used clinically as a defensive type anti-ulcer agent, has poor solubility and a bitter taste. To improve its solubility, a crystal engineering approach was proposed with the formation of novel salts using an artificial sweetener as a salt co-former. This was also expected to address the bitter taste of the drug. In this work, we report on the preparation and evaluation of the physicochemical properties of the novel salts benexate saccharinate monohydrate and benexate cyclamate whose crystal structures were determined by single-crystal X-ray structure analysis. These novel salts showed higher solubility and faster dissolution profiles that were associated with the occurrence of local layered-like structures. They also showed better moisture uptake profiles and were classified as non-hygroscopic materials. Therefore, benexate saccharinate monohydrate and benexate cyclamate expedited the development of sweet pharmaceutical salts of benexate with improved performances.

Background and Study Aims: Endoscopic submucosal dissection (ESD) has a high en bloc resection rate and is widely performed for large superficial colorectal tumors, but delayed bleeding remains one of the most common complications of colorectal ESD. The aim of the present study was to evaluate the clinical efficacy of prophylactic clip closure of mucosal defects for the prevention of delayed bleeding after colorectal ESD., Patients and Methods: We enrolled consecutive patients with colorectal lesions between January 2012 and May 2017 in this retrospective study. In the early part of this period, post-ESD mucosal defects were not closed (non-closure group); however, from January 2014, post-ESD mucosal defects were prophylactically closed with clips when possible (closure group). The main outcome measured was delayed bleeding. Variables were analyzed using the chi-squared test, Fisher's exact test, or Student's t-test., Results: Of 156 lesions analyzed, 61 were in the non-closure group and 95 in the closure group. Overall, delayed bleeding occurred in 5 cases (3.2 %). The delayed bleeding rate was 0 % (0/95) in the closure group and 8.2 % (5/61) in the non-closure group ( P  = 0.008). The mean procedure time for closure was 10.4 ± 4.6 min (range 3 - 26 min)., Conclusions: We demonstrated that prophylactic clip closure of mucosal defects might reduce the risk of delayed bleeding after colorectal ESD.

We report the first multicomponent crystal of desloratadine, an important anti-histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine-benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine-benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a co-receptor of the Wnt signalling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane - a process known as transcytosis. We show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL. LRP6 formed a complex with Niemann-Pick type C1-like 1 (NPC1L1), which is localized to the bile canalicular membrane of the liver and is involved in cholesterol absorption from the bile. LRP6 was required for apical membrane localization of NPC1L1 in the absence of LDL. Clathrin-dependent LRP6 internalization occurred in the presence of LDL, which resulted in trafficking of LRP6 to the lysosome, thereby reducing apical sorting of LRP6 and NPC1L1. These results suggest that LRP6 endocytosis proceeds by two routes, depending on the presence of LDL, and that LRP6 controls the intracellular destination of NPC1L1 in hepatocytes., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Epalerstat {systematic name: (5 Z )-5-[(2 E )-2-methyl-3-phenyl-prop-2-en-1-yl-idene]-4-oxo-2-sulfanyl-idene-1,3-thia-zolidine-3-acetic acid} crystallized as an acetone monosolvate, C 15 H 13 NO 3 S 2 ·C 3 H 6 O. In the epalerstat mol-ecule, the methyl-propyl-enediene moiety is inclined to the phenyl ring and the five-membered rhodamine ring by 21.4 (4) and 4.7 (4)°, respectively. In addition, the acetic acid moiety is found to be almost normal to the rhodamine ring, making a dihedral angle of 85.1 (2)°. In the crystal, a pair of O-H⋯O hydrogen bonds between the carb-oxy-lic acid groups of epalerstat mol-ecules form inversion dimers with an R 2 (20) loops, forming chains propagating along the [101] direction. In addition, the acetone mol-ecules are linked to the chain by a C-H⋯O hydrogen bond. Epalerstat acetone monosolvate was found to be isotypic with epalerstat tertra-hydro-furan solvate [Umeda 2 (8) loop. The dimers are linked by pairs of C-H⋯O hydrogen bonds, enclosing R 2 2 (20) loops, forming chains propagating along the [101] direction. In addition, the acetone mol-ecules are linked to the chain by a C-H⋯O hydrogen bond. Epalerstat acetone monosolvate was found to be isotypic with epalerstat tertra-hydro-furan solvate [Umeda et al. (2017 ▸). Acta Cryst . E 73 , 941-944].

The title compound, epalrestat {systematic name: (5 Z )-5-[(2 E )-2-methyl-3-phenyl-prop-2-en-1-yl-idene]-4-oxo-2-sulfanyl-idene-1,3-thia-zolidine-3-acetic acid}, crystallized as a tetra-hydro-furan monosolvate, C 15 H 13 NO 3 S 2 ·C 4 H 8 O. Epalrestat, an important drug for diabetic neuropathy, has been reported to exist in polymphic, solvated and co-crystal forms. In the mol-ecule reported here, the phenyl ring is inclined to the rhodamine ring by 22.31 (9)°, and the acetic acid group is almost normal to the rhodamine ring, making a dihedral angle of 88.66 (11)°. In the crystal, pairs of O-H⋯O hydrogen bonds are observed between the carb-oxy-lic acid groups of epalerstat mol-ecules, forming inversion dimers with an R 2 2 (8) loop. The dimers are linked by pairs of C-H⋯O hydrogen bonds, forming chains along [101]. The solvate mol-ecules are linked to the chain by a C-H⋯O(tetra-hydro-furan) hydrogen bond. A combination of thermal analysis and powder X-ray diffraction revealed that title compound desolvated into epalerstat Form II. One C atom of the tetra-hydro-furan solvate mol-ecule is positionally disordered and has a refined occupancy ratio of 0.527 (18):0.473 (18).

The Ras/Raf/MEK/ERK pathway has been identified as a major, druggable regulator of melanoma. Mutational activation of BRAF is the most prevalent genetic alteration in human melanoma, resulting in constitutive melanoma hyperproliferation. A selective BRAF inhibitor showed remarkable clinical activity in patients with mutated BRAF. Unfortunately, most patients acquire resistance to the BRAF inhibitor, highlighting the urgent need for new melanoma treatment strategies. Green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) inhibits cell proliferation independently of BRAF inhibitor sensitivity, suggesting that increased understanding of the anti-melanoma activity of EGCG may provide a novel therapeutic target. Here, by performing functional genetic screening, we identified protein phosphatase 2A (PP2A) as a critical factor in the suppression of melanoma cell proliferation. We demonstrated that tumor-overexpressed 67-kDa laminin receptor (67LR) activates PP2A through adenylate cyclase/cAMP pathway eliciting inhibitions of oncoproteins and activation of tumor suppressor Merlin. Activating 67LR/PP2A pathway leading to melanoma-specific mTOR inhibition shows strong synergy with the BRAF inhibitor PLX4720 in the drug-resistant melanoma. Moreover, SET, a potent inhibitor of PP2A, is overexpressed on malignant melanoma. Silencing of SET enhances 67LR/PP2A signaling. Collectively, activation of 67LR/PP2A signaling may thus be a novel rational strategy for melanoma-specific treatment., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

One of the flavones, apigenin has various physiological functions including anti-inflammatory activities. Atopic dermatitis (AD) is a chronically relapsing inflammatory disorder that is characterized by pruritic and eczematous skin lesions. To evaluate the anti-allergic effect of apigenin in vivo, we examined the effect of dietary apigenin on picrylchloride (PiCl)-induced AD-like pathology in NC/Nga mice. NC/Nga mice were fed experimental diets containing apigenin from Day 18 after sensitized with PiCl for 4 weeks. Dietary apigenin significantly alleviated the development of skin lesions, accompanied by lower serum immunoglobulin (Ig) G1 and IgE levels in NC/Nga mice. Interferon (IFN)-gamma mRNA expression level in spleen cells from NC/Nga mice was reduced by apigenin feeding. Moreover, interleukin 4-induced signal transducers and activators of transcription 6 phosphorylation in primary spleen cells from BALB/c mice was inhibited by treatment with apigenin. These results suggest that apigenin attenuates exacerbation of AD-like symptoms in part through the reduction of serum IgE level and IFN-gamma expression in NC/Nga mice.

H89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) is a compound characterized in vitro as a potent and selective inhibitor of protein kinase A (PKA). In this study, we found that H89 reduced the phosphorylation of the myosin regulatory light chain (MRLC) at Thr-18/Ser-19 and induced disassembly of stress fibers in HeLa cells. In addition, we found that H89 induced not only reduction of the MRLC phosphorylation but also cell growth inhibition in several human cancer cell lines. Recently H89 has been found to inhibit Rho-kinase with potency similar to or greater than that for inhibition of PKA. Indeed, the effects of H89 on both the MRLC phosphorylation and actin cytoskeleton organization were nearly identical to those of Rho-kinase inhibitor Y-27632. However, unlike H89, Y-27632 did not affect cell growth of HeLa cells. Further, when the myosin phosphatase targeting subunit 1 (MYPT1) expression was silenced by RNA interference in HeLa cells, the suppressive effect of H89 on the MRLC phosphorylation was not affected, while H89-induced cell growth inhibition was blocked. These results suggest that H89-induced reduction of the MRLC phosphorylation results from inhibition of Rho-kinase and that H89-induced cell growth inhibition is independent of reduction of the MRLC phosphorylation.

Here, we investigated the structure-activity relationship of major green tea catechins and their corresponding epimers on cell-surface binding and inhibitory effect on histamine release. Galloylated catechins; (-)-epigallocatechin-3-O-gallate (EGCG), (-)-gallocatechin-3-O-gallate (GCG), (-)-epicatechin-3-O-gallate (ECG), and (-)-catechin-3-O-gallate (CG) showed the cell-surface binding to the human basophilic KU812 cells by surface plasmon resonance analysis, but their non-galloylated forms did not. Binding activities of pyrogallol-type catechins (EGCG and GCG) were higher than those of catechol-type catechins (ECG and CG). These patterns were also observed in their inhibitory effects on histamine release. Previously, we have reported that biological activities of EGCG are mediated through the binding to the cell-surface 67kDa laminin receptor (67LR). Downregulation of 67LR expression caused a reduction of both activities of galloylated catechins. These results suggest that both the galloyl moiety and the B-ring hydroxylation pattern contribute to the exertion of biological activities of tea catechins and their 67LR-dependencies.

Previously we reported that 67-kDa laminin receptor (67LR) mediates epigallocatechin-3-O-gallate (EGCG)-induced cell growth inhibition and reduction of myosin regulatory light chain (MRLC) phosphorylation at Thr-18/Ser-19, which is important for cytokinesis. Here, we found that human colon adenocarcinoma Caco-2 cells exhibited higher expression level of 67LR and EGCG at a physiologically achievable concentration (1 microM) significantly accumulated the cells in G(2)/M phase without affecting expression of Wnt-signaling components. We also found that myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation at Thr-696, which inhibits myosin phosphatase and promotes MRLC phosphorylation, was reduced in response to 1 microM EGCG. 67LR knockdown by RNA interference abolished the inhibitory effects of 1 microM EGCG on cell cycle progression and the phosphorylation of MRLC and MYPT1. These results suggest that through 67LR, EGCG at a physiological concentration can activate myosin phosphatase by reducing MYPT1 phosphorylation and that may be involved in EGCG-induced cell growth inhibition.

(-)-Epigallocatechin-3-gallate (EGCG), the principal polyphenol in green tea, has been shown to be a potent chemopreventive agent. Recently, 67-kDa laminin receptor (67LR) has been identified as a cell surface receptor for EGCG that mediates the anticancer activity of EGCG. Indeed, expression of 67LR confers EGCG responsiveness to tumor cells; however, the molecular basis for the anticancer activity of EGCG in vivo is not entirely understood. Here we show that (i) using a direct genetic screen, eukaryotic translation elongation factor 1A (eEF1A) is identified as a component responsible for the anticancer activity of EGCG; (ii) through both eEF1A and 67LR, EGCG induces the dephosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) at Thr-696 and activates myosin phosphatase; and (iii) silencing of 67LR, eEF1A, or MYPT1 in tumor cells results in abrogation of EGCG-induced tumor growth inhibition in vivo. Additionally, we found that eEF1A is up-regulated by EGCG through 67LR. Overall, these findings implicate both eEF1A and MYPT1 in EGCG signaling for cancer prevention through 67LR.

Previously we have reported that the O-methylated derivative of (-)-epigallocatechin-3-O-gallate (EGCG), (-)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me), possesses anti-allergic activities such as inhibition of histamine release and suppression of the high-affinity IgE receptor (FcepsilonRI) expression. However, the underlying mechanism is still unclear. Recently we have identified the 67kDa laminin receptor (67LR) as a cell-surface receptor that can mediate biological activities of EGCG. Here we show that the suppression of myosin II regulatory light chain (MRLC) phosphorylation through the cell-surface binding to the 67 LR contributes to the inhibitory effect of EGCG3"Me on the histamine release from the human basophilic KU812 cells. The 67LR also mediated the EGCG3"Me-induced suppression of FcepsilonRI expression by reducing ERK1/2 phosphorylation. These results suggest that anti-allergic effects of EGCG3"Me may be triggered by the inhibition of MRLC or ERK1/2 phosphorylation mediated through the cell-surface 67LR.

It was previously reported that (-)-epigallocatechin-3-O-gallate (EGCG) suppresses the expression of the high-affinity IgE receptor FcepsilonRI in human basophilic cells and that this suppressive effect is associated with EGCG binding to the cell surface. This study examined the effects of five methylated derivatives of EGCG, (-)-epigallocatechin-3-O-(3-O-methyl)gallate (EGCG 3' 'Me), (-)-epigallocatechin-3-O-(4-O-methyl)gallate (EGCG 4' 'Me), (-)-4'-O-methyl-epigallocatechin-3-O-gallate (EGCG 4'Me), (-)-epigallocatechin-3-O-(3,4-O-methyl)gallate (EGCG 3' '4' 'diMe), and (-)-4'-O-methyl-epigallocatechin-3-O-(4-O-methyl)gallate (EGCG 4'4' 'diMe) on FcepsilonRI expression and ERK1/2 phosphorylation, and each of their cell surface binding activities was measured. Of these five methylated derivatives, three that are methylated at the 3' '- and/or 4' '-position, EGCG 3' 'Me, EGCG 4' 'Me, and EGCG 3' '4' 'diMe, suppressed FcepsilonRI expression and ERK1/2 phosphorylation, although the suppressive effects were lower than that of EGCG. EGCG 4'Me and EGCG 4'4' 'diMe, both of which are methylated at the 4'-position, did not demonstrate a suppressive effect. Furthermore, it was found that EGCG 3' 'Me, EGCG 4' 'Me, EGCG 3' '4' 'diMe, and EGCG 4'Me, which are methylated at the 3' '- and/or 4' '-positions or the 4'-position, could bind to the cell surface even though their binding activities were lower than that of EGCG. Only EGCG 4'4' 'diMe, which is methylated at both the 4'- and 4' '-positions, could not bind. These results suggest that the trihydroxyl structure of the B ring is essential for EGCG to exert the suppressive effects and that the hydroxyl groups on both the 4'-position in the B ring and the 4' '-position in the gallate are crucial for the cell surface binding activity of EGCG.

Background: The flavonoids are a diverse family of chemicals commonly found in fruits and vegetables. Previously, we have shown that the two flavones, chrysin and apigenin could suppress the expression of the high affinity IgE receptor FcepsilonRI in human basophilic KU812 cells. We also demonstrated that dietary apigenin decreased IgE level in C57BL/6N mice sera., Aim of the Study: To evaluate the anti-allergic effect of the two flavones in vivo, we evaluated the effect of the two flavones, chrysin and apigenin, on the immune system in BALB/c mice sensitized with ovalbumin (OVA)., Methods: Mice were fed experimental diets containing either of the flavones for 3 weeks and immunized with OVA. After the experimental feeding period, measurement of Igs concentration in the mice sera was performed using a sandwich ELISA. Cytokines expression in mice sera was assessed using a cytokine array. Furthermore, cytokines mRNA levels in spleen lymphocytes from mice sensitized with OVA were measured by RT-PCR., Results: The total IgE level in mice fed one of the two flavones were suppressed, whereas levels of IgG, IgM, and IgA were not affected. The production of interleukin (IL)-4, which is known as one of Th2 cytokines and regulates the production of IgE, was down-regulated by the chrysin or the apigenin diet. Moreover, OVA-induced mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin diet., Conclusions: The results suggest that the diet containing one of the two flavones might suppress the up-regulation of serum IgE induced by OVA-immunization through the suppression of Th2-type immune response.

Recently, we have reported that (-)-epigallocatechin-3-O-gallate (EGCG) acts as an inhibitor of degranulation. However, the inhibitory mechanism for degranulation is still poorly understood. Here we show that suppression of exocytosis-related myosin II regulatory light chain phosphorylation and alteration of actin remodeling are involved in the inhibitory effect of EGCG on the calcium ionophore-induced degranulation from human basophilic KU812 cells. Surface plasmon resonance assay also revealed that EGCG binds to the cell surface, and the disruption of lipid rafts resulted in reduction of EGCG's ability. We have previously identified the raft-associated 67kDa laminin receptor (67LR) as an EGCG receptor on the cell surface. Treatment of the cells with anti-67LR antibody or RNA interference-mediated downregulation of 67LR expression abolished the effects of EGCG. These findings suggest that EGCG-induced inhibition of the degranulation includes the primary binding of EGCG to the cell surface 67LR and subsequent modulation of cytoskeleton.

Flavonoids ubiquitously exist in plants, vegetables, fruits, and teas. We evaluated the effect of dietary apigenin, one of the well-known flavonoids, on the immune system in C57BL/6N mice. Mice were fed experimental diets containing apigenin for 2 weeks. After the experimental period, there was no significant difference in body and organ weights between the control and the apigenin group. The total immunoglobulin (Ig) E levels in mice fed apigenin were significantly suppressed, whereas levels of IgG, IgM, and IgA were not affected. We also examined the effect of the apigenin diet on cytokine expression in mice sera using a cytokine array. The production of regulated upon activation normal T cell expressed and secreted (RANTES) and soluble tumor necrosis factor receptor I (sTNFRI) in mice sera was down-regulated by the apigenin diet. These results suggest that a diet containing apigenin can reduce serum IgE and inflammatory cytokines such as RANTES and sTNFRI in mice.

Epigallocatechin-3-O-gallate (EGCG), a major polyphenol of green tea, has been shown to inhibit the growth of various cancer cell lines. We show here that EGCG induced the disruption of stress fibers and decreased the phosphorylation of the myosin II regulatory light chain (MRLC) at Thr18/Ser19, which is necessary for both contractile ring formation and cell division. Indirect immunofluorescence analysis revealed that EGCG inhibited the concentration of both F-actin and the phosphorylated MRLC in the cleavage furrow at the equator of dividing cells. In addition, EGCG increased the percentages of cells in the G(2)/M phase and inhibited cell growth. Recently, we have demonstrated that the anticancer activity of EGCG is mediated by the metastasis-associated 67kDa laminin receptor (67LR). To explore whether the effect of EGCG is mediated by the 67LR, we transfected cells with short hairpin RNA (shRNA) expression vector to downregulate 67LR expression. When the 67LR was silenced, the suppressive effect of EGCG on the MRLC phosphorylation was significantly attenuated. These results suggest that EGCG inhibits the cell growth by reducing the MRLC phosphorylation and this effect is mediated by the 67LR.

Phosphorylation of myosin II regulatory light chain (MRLC) is critical event for many cellular processes including muscle contraction, mytosis, migration, and exocytosis. Epigallocatechin-3-O-gallate (EGCG) is a major polyphenolic compound of green tea and has various physiological functions. We found that EGCG disrupted stress fibers and suppressed the MRLC phosphorylation in HeLa cells. To elucidate the mechanism for the suppressive effect on the phosphorylation, we examined the effect of various inhibitors for kinases that modulate MRLC phosphorylation. None of the inhibitors mimic the activity of EGCG. These results suggest that EGCG is a compound that can suppress MRLC phosphorylation.