Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50 concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.
{"title":"High concentration calcitriol induces endoplasmic reticulum stress related gene profile in breast cancer cells.","authors":"A. Ozkaya, Handan Ak, H. Aydin","doi":"10.1139/bcb-2016-0037","DOIUrl":"https://doi.org/10.1139/bcb-2016-0037","url":null,"abstract":"Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50 concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"326 1","pages":"289-294"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91229039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Gajalakshmi, Syamantak Majumder, C. Viebahn, Akila Swaminathan, G. Yeoh, S. Chatterjee
Liver fibrosis is now well recognized as the causative factor for increased mortality from complications associated with liver pathologies. Activated hepatic stellate cells (HSCs) play a critical role in the progression of liver fibrosis. Therefore, targeting these activated HSCs to prevent and (or) treat liver disease is a worthwhile approach to explore. In the present in vitro study, we investigated the use of bipotential murine oval liver cells (BMOL) in regulating the functions of activated HSCs to prevent progression of liver fibrosis. We used a conditioned medium-based approach to study the effect of BMOL cells on activated HSC survival and function. Our data showed that BMOL cells block the contraction of activated HSCs by inducing apoptosis of these cells. We demonstrated that BMOL cells secrete soluble factors, such as interleukin-6 (IL-6), which induced apoptosis of activated HSCs. Using both pharmacological and molecular inhibitor approaches, we further identified that IL-6-mediated activation of NF-κB-iNOS-NO-ROS signaling in activated HSCs plays a critical role in BMOL-cell-mediated apoptosis of activated HSCs. Thus, the present study provides an alternative cell-based therapeutic approach to treat liver fibrosis.
{"title":"Interleukin-6 secreted by bipotential murine oval liver stem cells induces apoptosis of activated hepatic stellate cells by activating NF-κB-inducible nitric oxide synthase signaling.","authors":"P. Gajalakshmi, Syamantak Majumder, C. Viebahn, Akila Swaminathan, G. Yeoh, S. Chatterjee","doi":"10.1139/bcb-2016-0011","DOIUrl":"https://doi.org/10.1139/bcb-2016-0011","url":null,"abstract":"Liver fibrosis is now well recognized as the causative factor for increased mortality from complications associated with liver pathologies. Activated hepatic stellate cells (HSCs) play a critical role in the progression of liver fibrosis. Therefore, targeting these activated HSCs to prevent and (or) treat liver disease is a worthwhile approach to explore. In the present in vitro study, we investigated the use of bipotential murine oval liver cells (BMOL) in regulating the functions of activated HSCs to prevent progression of liver fibrosis. We used a conditioned medium-based approach to study the effect of BMOL cells on activated HSC survival and function. Our data showed that BMOL cells block the contraction of activated HSCs by inducing apoptosis of these cells. We demonstrated that BMOL cells secrete soluble factors, such as interleukin-6 (IL-6), which induced apoptosis of activated HSCs. Using both pharmacological and molecular inhibitor approaches, we further identified that IL-6-mediated activation of NF-κB-iNOS-NO-ROS signaling in activated HSCs plays a critical role in BMOL-cell-mediated apoptosis of activated HSCs. Thus, the present study provides an alternative cell-based therapeutic approach to treat liver fibrosis.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"33 1","pages":"263-272"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78427763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase, and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation owing to the toxic build-up of the deglycase substrate. The limited distribution of this metabolic pathway in the animal gut microbiome raises the prospects for antibacterial discovery. We report the biochemical characterization of the kinase that was expected to transform fructose-aspartate to 6-phosphofructose-aspartate during F-Asn utilization. In addition to confirming its anticipated function, we determined through studies of fructose-aspartate analogues that this kinase exhibits a substrate-specificity with greater tolerance to changes to the amino acid (including the d-isomer of aspartate) than to the sugar.
{"title":"Characterization of a Salmonella sugar kinase essential for the utilization of fructose-asparagine.","authors":"P. Biswas, E. Behrman, V. Gopalan","doi":"10.1139/bcb-2016-0138","DOIUrl":"https://doi.org/10.1139/bcb-2016-0138","url":null,"abstract":"Salmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase, and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation owing to the toxic build-up of the deglycase substrate. The limited distribution of this metabolic pathway in the animal gut microbiome raises the prospects for antibacterial discovery. We report the biochemical characterization of the kinase that was expected to transform fructose-aspartate to 6-phosphofructose-aspartate during F-Asn utilization. In addition to confirming its anticipated function, we determined through studies of fructose-aspartate analogues that this kinase exhibits a substrate-specificity with greater tolerance to changes to the amino acid (including the d-isomer of aspartate) than to the sugar.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"44 1","pages":"304-309"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90726177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT-β-catenin pathway. The upregulation of Wnt6 and activation of β-catenin-TCF-LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the 10 Fzd genes were found to be expressed in F9 cells, with Fzd7 being the most highly expressed, and chosen for further analysis. To alter steady-state Fzd7 levels and test the effect this has on differentiation, siRNA and overexpression approaches were used to knock-down and ectopically express the Fzd7 message, respectively. siRNA knock-down of Fzd7 resulted in reduced DAB2 levels, and the overexpression activated a TCF-LEF reporter, but neither approach affected differentiation. Our focus turned to how canonical WNT6 signaling was attenuated to allow PrE cells to form parietal endoderm (PE). Dkk1, encoding a WNT antagonist, was examined and results showed that its expression increased in F9 cells treated with retinoic acid (RA) or overexpressing Wnt6. F9 cells overexpressing human DKK1 or treated with DKK1-conditioned medium and then treated with RA failed to differentiate, indicating that a negative feedback loop involving WNT6 and DKK1 attenuates canonical WNT-β-catenin signaling, thereby allowing PE cells to differentiate.
{"title":"Frizzled gene expression and negative regulation of canonical WNT-β-catenin signaling in mouse F9 teratocarcinoma cells.","authors":"Gregory Golenia, Mohamed I. Gatie, G. Kelly","doi":"10.1139/bcb-2016-0150","DOIUrl":"https://doi.org/10.1139/bcb-2016-0150","url":null,"abstract":"Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT-β-catenin pathway. The upregulation of Wnt6 and activation of β-catenin-TCF-LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the 10 Fzd genes were found to be expressed in F9 cells, with Fzd7 being the most highly expressed, and chosen for further analysis. To alter steady-state Fzd7 levels and test the effect this has on differentiation, siRNA and overexpression approaches were used to knock-down and ectopically express the Fzd7 message, respectively. siRNA knock-down of Fzd7 resulted in reduced DAB2 levels, and the overexpression activated a TCF-LEF reporter, but neither approach affected differentiation. Our focus turned to how canonical WNT6 signaling was attenuated to allow PrE cells to form parietal endoderm (PE). Dkk1, encoding a WNT antagonist, was examined and results showed that its expression increased in F9 cells treated with retinoic acid (RA) or overexpressing Wnt6. F9 cells overexpressing human DKK1 or treated with DKK1-conditioned medium and then treated with RA failed to differentiate, indicating that a negative feedback loop involving WNT6 and DKK1 attenuates canonical WNT-β-catenin signaling, thereby allowing PE cells to differentiate.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"130 1","pages":"251-262"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73143938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fraser G Ferens, V. Spicer, O. Krokhin, A. Motnenko, W. Summers, D. A. Court
Mitochondrial porin, the voltage-dependent anion channel, plays an important role in metabolism and other cellular functions within eukaryotic cells. To further the understanding of porin structure and function, Neurospora crassa wild-type porin was replaced with a deletion variant lacking residues 238-242 (238porin). 238porin was assembled in the mitochondrial outer membrane, but the steady state levels were only about 3% of those of the wild-type protein. The strain harbouring 238porin displayed cytochrome deficiencies and expressed alternative oxidase. Nonetheless, it exhibited an almost normal linear growth rate. Analysis of mitochondrial proteomes from a wild-type strain FGSC9718, a strain lacking porin (ΔPor-1), and one expressing only 238porin, revealed that the major differences between the variant strains were in the levels of subunits of the NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain, which were reduced only in the ΔPor-1 strain. These, and other proteins related to electron flow and mitochondrial biogenesis, are differentially affected by relative porin levels.
{"title":"A deletion variant partially complements a porin-less strain of Neurospora crassa.","authors":"Fraser G Ferens, V. Spicer, O. Krokhin, A. Motnenko, W. Summers, D. A. Court","doi":"10.1139/bcb-2016-0166","DOIUrl":"https://doi.org/10.1139/bcb-2016-0166","url":null,"abstract":"Mitochondrial porin, the voltage-dependent anion channel, plays an important role in metabolism and other cellular functions within eukaryotic cells. To further the understanding of porin structure and function, Neurospora crassa wild-type porin was replaced with a deletion variant lacking residues 238-242 (238porin). 238porin was assembled in the mitochondrial outer membrane, but the steady state levels were only about 3% of those of the wild-type protein. The strain harbouring 238porin displayed cytochrome deficiencies and expressed alternative oxidase. Nonetheless, it exhibited an almost normal linear growth rate. Analysis of mitochondrial proteomes from a wild-type strain FGSC9718, a strain lacking porin (ΔPor-1), and one expressing only 238porin, revealed that the major differences between the variant strains were in the levels of subunits of the NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain, which were reduced only in the ΔPor-1 strain. These, and other proteins related to electron flow and mitochondrial biogenesis, are differentially affected by relative porin levels.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"13 1","pages":"318-327"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79126461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lactoferrin researchers descend on Nagoya Castle.","authors":"D. Alexander, H. Vogel, H. Tsuda","doi":"10.1139/bcb-2017-0009","DOIUrl":"https://doi.org/10.1139/bcb-2017-0009","url":null,"abstract":"","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"38 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76979780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yung‐An Tsou, Y. Tung, Tsu-Fang Wu, G. Chang, Han-Chien Chen, Chia-Der Lin, Chih-Ho Lai, Hsiao‐Ling Chen, Chuan‐Mu Chen
The short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an important innate material in the upper airway, and lactoferrin (LF) aids the innate functions in humans. In this study, a nasal epithelial model was used to investigate how LF modulates SPLUNC1 to reduce the inflammatory process mediated by lipopolysaccharide (LPS). The inflammation of human RPMI-2650 cells was induced with LPS to evaluate SPLUNC1 expression after treating the cells with bovine LF (bLF). The interaction pathway between LF and SPLUNC1 in LPS-induced inflammation was further investigated. Our study reveals that the addition of bLF results in the recovery of SPLUNC1 expression in nasal epithelial cells under LPS-induced inflammation. MAPK is involved in the main pathway for the SPLUNC1 and bLF interaction. Decreased SPLUNC1 function could be recovered by addition of bLF. The MEK1/2-MAPK signaling pathway is crucial for the SPLUNC1 and bLF interaction. Therefore, LF could support SPLUNC1 in the innate immunity recovery process.
{"title":"Lactoferrin interacts with SPLUNC1 to attenuate lipopolysaccharide-induced inflammation of human nasal epithelial cells via down-regulated MEK1/2-MAPK signaling.","authors":"Yung‐An Tsou, Y. Tung, Tsu-Fang Wu, G. Chang, Han-Chien Chen, Chia-Der Lin, Chih-Ho Lai, Hsiao‐Ling Chen, Chuan‐Mu Chen","doi":"10.1139/bcb-2016-0047","DOIUrl":"https://doi.org/10.1139/bcb-2016-0047","url":null,"abstract":"The short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an important innate material in the upper airway, and lactoferrin (LF) aids the innate functions in humans. In this study, a nasal epithelial model was used to investigate how LF modulates SPLUNC1 to reduce the inflammatory process mediated by lipopolysaccharide (LPS). The inflammation of human RPMI-2650 cells was induced with LPS to evaluate SPLUNC1 expression after treating the cells with bovine LF (bLF). The interaction pathway between LF and SPLUNC1 in LPS-induced inflammation was further investigated. Our study reveals that the addition of bLF results in the recovery of SPLUNC1 expression in nasal epithelial cells under LPS-induced inflammation. MAPK is involved in the main pathway for the SPLUNC1 and bLF interaction. Decreased SPLUNC1 function could be recovered by addition of bLF. The MEK1/2-MAPK signaling pathway is crucial for the SPLUNC1 and bLF interaction. Therefore, LF could support SPLUNC1 in the innate immunity recovery process.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"117 1","pages":"394-399"},"PeriodicalIF":0.0,"publicationDate":"2017-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76685650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Takayama, R. Aoki, Ryo Uchida, A. Tajima, A. Aoki-Yoshida
Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K-Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling.
{"title":"Role of CXC chemokine receptor type 4 as a lactoferrin receptor.","authors":"Y. Takayama, R. Aoki, Ryo Uchida, A. Tajima, A. Aoki-Yoshida","doi":"10.1139/bcb-2016-0039","DOIUrl":"https://doi.org/10.1139/bcb-2016-0039","url":null,"abstract":"Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K-Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"66 1","pages":"57-63"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75331039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.
{"title":"Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways.","authors":"Rulan Jiang, B. Lönnerdal","doi":"10.1139/bcb-2016-0094","DOIUrl":"https://doi.org/10.1139/bcb-2016-0094","url":null,"abstract":"Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"57 1","pages":"99-109"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74204221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. T. Rahideh, M. Keramatipour, M. Nourbakhsh, F. Koohdani, M. Hoseini, S. Talebi, F. Shidfar
Nobiletin (NOB) is one of the polymethoxyflavones mainly found in citrus fruits. Aromatase or cytochrome P450 (CYP19) enzyme catalyzes the last and rate-limiting step in estrogen biosynthesis. This study was carried out to investigate the effect of NOB on the activity and expression of aromatase, and to compare this property with letrozole (LET) as aromatase inhibitor in the MCF-7 breast cancer cell line. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays. Aromatase enzyme activity based on the conversion of androgenic substrate testosterone into 17β-estradiol was determined. CYP19 gene expression was measured by quantitative real-time PCR. MTT assays demonstrated that NOB at a concentration of 100 μmol/L decreased cell viability in a time-dependent manner (P < 0.05). NOB significantly inhibited aromatase at the concentration of 0.1 μmol/L (P = 0.013), whereas other concentrations had no effect. Treatment with 10 μmol/L and 1 μmol/L of NOB for 48 h significantly increased (P = 0.001) and decreased (P = 0.02) relative aromatase expression, respectively. The combination of LET and NOB had no effect on aromatase. This study showed for the first time that NOB decreases the activity and expression of aromatase at low concentrations in MCF-7 breast cancer cells.
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