Pub Date : 2022-06-30DOI: 10.15430/JCP.2022.27.2.101
Eun-Ryeong Hahm, Sivapar V Mathan, Rana P Singh, Shivendra V Singh
Diallyl trisulfide (DATS) is an attractive anti-cancer phytochemical with in vitro and in vivo growth inhibitory effects against different solid tumors including breast cancer. We have shown previously that an immortalized mammary epithelial cell line (MCF-10A) is resistant to growth inhibition by DATS. In this study, we performed RNA-seq analysis using a breast cancer cell line (SK-BR-3) and MCF-10A cells to gain insights into cancer selective effects of DATS. The Gene Ontology analysis revealed upregulation of genes associated with actin cytoskeleton but downregulation of mitochondria-related genes in the SK-BR-3 human breast cancer cell line but not in the non-oncogenic MCF-10A cell line upon treatment with DATS. Quantitative real-time reverse transcription polymerase chain reaction confirmed DATS-mediated upregulation of several actin cytoskeleton-related genes in the SK-BR-3 cell line. The DATS treatment dose-dependently disrupted actin cytoskeleton in the SK-BR-3 cell line, whereas the MCF-10A cell line was more resistant to this effect. The DATS treatment caused a marked increase in phosphorylation of dynamin-1-like (DRP1) protein in the SK-BR-3 cell line. However, the DATS-mediated apoptosis was not affected by genetic deletion of DRP1 protein. The Reactome pathway analysis showed downregulation of genes associated with citric acid cycle in the SK-BR-3 cell line but not in the MCF-10A cells. However, expression of aconitase 2 or dihydrolipoamide S-succinyltransferase was not affected by DATS treatment. In conclusion, this study reveals that actin cytoskeleton is a novel target of DATS in the SK-BR-3 cell line, which may explain its inhibitory effect on breast cancer cell migration.
{"title":"Breast Cancer Selective Disruption of Actin Cytoskeleton by Diallyl Trisulfide.","authors":"Eun-Ryeong Hahm, Sivapar V Mathan, Rana P Singh, Shivendra V Singh","doi":"10.15430/JCP.2022.27.2.101","DOIUrl":"10.15430/JCP.2022.27.2.101","url":null,"abstract":"<p><p>Diallyl trisulfide (DATS) is an attractive anti-cancer phytochemical with in vitro and in vivo growth inhibitory effects against different solid tumors including breast cancer. We have shown previously that an immortalized mammary epithelial cell line (MCF-10A) is resistant to growth inhibition by DATS. In this study, we performed RNA-seq analysis using a breast cancer cell line (SK-BR-3) and MCF-10A cells to gain insights into cancer selective effects of DATS. The Gene Ontology analysis revealed upregulation of genes associated with actin cytoskeleton but downregulation of mitochondria-related genes in the SK-BR-3 human breast cancer cell line but not in the non-oncogenic MCF-10A cell line upon treatment with DATS. Quantitative real-time reverse transcription polymerase chain reaction confirmed DATS-mediated upregulation of several actin cytoskeleton-related genes in the SK-BR-3 cell line. The DATS treatment dose-dependently disrupted actin cytoskeleton in the SK-BR-3 cell line, whereas the MCF-10A cell line was more resistant to this effect. The DATS treatment caused a marked increase in phosphorylation of dynamin-1-like (DRP1) protein in the SK-BR-3 cell line. However, the DATS-mediated apoptosis was not affected by genetic deletion of DRP1 protein. The Reactome pathway analysis showed downregulation of genes associated with citric acid cycle in the SK-BR-3 cell line but not in the MCF-10A cells. However, expression of aconitase 2 or dihydrolipoamide S-succinyltransferase was not affected by DATS treatment. In conclusion, this study reveals that actin cytoskeleton is a novel target of DATS in the SK-BR-3 cell line, which may explain its inhibitory effect on breast cancer cell migration.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 2","pages":"101-111"},"PeriodicalIF":2.5,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/40/jcp-27-2-101.PMC9271405.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40613409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.50
Athena Dong, Chien-Wei Lin, Carla Elena Echeveste, Yi-Wen Huang, Kiyoko Oshima, Martha Yearsley, Xiao Chen, Jianhua Yu, Li-Shu Wang
Administration of black raspberries (BRBs) and their anthocyanin metabolites, including protocatechuic acid (PCA), has been demonstrated to exert chemopreventive effects against colorectal cancer through alteration of innate immune cell trafficking, modulation of metabolic and inflammatory pathways, etc. Previous research has shown that the gut microbiome is important in the effectiveness of chemoprevention of colorectal cancer. This study aimed to assess the potency of PCA versus BRB dietary administration for colorectal cancer prevention using an ApcMin/+ mouse model and determine how bacterial profiles change in response to PCA and BRBs. A control AIN-76A diet supplemented with 5% BRBs, 500 ppm PCA, or 1,000 ppm PCA was administered to ApcMin/+ mice. Changes in incidence, polyp number, and polyp size regarding adenomas of the small intestine and colon were assessed after completion of the diet regimen. There were significant decreases in adenoma development by dietary administration of PCA and BRBs in the small intestine and the 5% BRB-supplemented diet in the colon. Pro-inflammatory bacterial profiles were replaced with anti-inflammatory bacteria in all treatments, with the greatest effects in the 5% BRB and 500 ppm PCA-supplemented diets accompanied by decreased COX-2 and prostaglandin E2 levels in colonic mucosa. We further showed that 500 ppm PCA, but not 1,000 ppm PCA, increased IFN-γ and SMAD4 levels in primary cultured human natural killer cells. These results suggest that both BRBs and a lower dose PCA can benefit colorectal cancer patients by inhibiting the growth and proliferation of adenomas and promoting a more favorable gut microbiome condition.
{"title":"Protocatechuic Acid, a Gut Bacterial Metabolite of Black Raspberries, Inhibits Adenoma Development and Alters Gut Microbiome Profiles in <i>Apc</i> <sup><i>Min</i>/+</sup> Mice.","authors":"Athena Dong, Chien-Wei Lin, Carla Elena Echeveste, Yi-Wen Huang, Kiyoko Oshima, Martha Yearsley, Xiao Chen, Jianhua Yu, Li-Shu Wang","doi":"10.15430/JCP.2022.27.1.50","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.50","url":null,"abstract":"<p><p>Administration of black raspberries (BRBs) and their anthocyanin metabolites, including protocatechuic acid (PCA), has been demonstrated to exert chemopreventive effects against colorectal cancer through alteration of innate immune cell trafficking, modulation of metabolic and inflammatory pathways, etc. Previous research has shown that the gut microbiome is important in the effectiveness of chemoprevention of colorectal cancer. This study aimed to assess the potency of PCA versus BRB dietary administration for colorectal cancer prevention using an <i>Apc</i> <sup><i>Min</i>/+</sup> mouse model and determine how bacterial profiles change in response to PCA and BRBs. A control AIN-76A diet supplemented with 5% BRBs, 500 ppm PCA, or 1,000 ppm PCA was administered to <i>Apc</i> <sup><i>Min</i>/+</sup> mice. Changes in incidence, polyp number, and polyp size regarding adenomas of the small intestine and colon were assessed after completion of the diet regimen. There were significant decreases in adenoma development by dietary administration of PCA and BRBs in the small intestine and the 5% BRB-supplemented diet in the colon. Pro-inflammatory bacterial profiles were replaced with anti-inflammatory bacteria in all treatments, with the greatest effects in the 5% BRB and 500 ppm PCA-supplemented diets accompanied by decreased COX-2 and prostaglandin E<sub>2</sub> levels in colonic mucosa. We further showed that 500 ppm PCA, but not 1,000 ppm PCA, increased IFN-γ and SMAD4 levels in primary cultured human natural killer cells. These results suggest that both BRBs and a lower dose PCA can benefit colorectal cancer patients by inhibiting the growth and proliferation of adenomas and promoting a more favorable gut microbiome condition.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"50-57"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/a8/jcp-27-1-50.PMC8984655.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.22
Eun-Ryeong Hahm, Shivendra V. Singh
Diallyl trisulfide (DATS) was shown to be a potent inhibitor of luminal-type MCF-7 xenograft growth in vivo. The present study was conducted to determine the preventive effect of DATS administration using an N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor model, which shares molecular resemblance to luminal-type human breast cancers. The DATS administration (50 mg/kg body weight, 5 times/week) was safe, but did not reduce mammary tumor latency, incidence, burden or multiplicity. Therefore, we conducted RNA-seq analysis using mammary tumors from control and DATS-treated rats (n = 3 for each group) to gain insights into lack of mammary tumor prevention by this phytochemical. The gene ontology and the Kyoto encyclopedia of genes and genomes pathway analyses of the RNA-seq data revealed upregulation of genes associated with ribosomes, translation, peptide biosynthetic/metabolic process, and oxidative phosphorylation but downregulation of genes associated with mitogen-activated protein kinases. A total of 33 genes associated with ribosomes were significantly upregulated by DATS treatment, including RPL11 and RPS14. Western blotting confirmed upregulation of RPL11 and neurofascin protein expression in mammary tumors from DATS-treated rats when compared to controls. A statistically significant increase in protein level of c-Jun N-terminal kinase 2 was also observed in tumors from DATS-treated rats when compared to controls. On the other hand, expression of complex I subunits NDUFV1 or NDUFS1 was not affected by DATS treatment. These results offer potential explanations for ineffectiveness of DATS in the chemically-induced rat mammary tumor model. Inhibitors of the proteins upregulated by DATS may be needed to improve chemopreventive efficacy of this phytochemical.
{"title":"Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats","authors":"Eun-Ryeong Hahm, Shivendra V. Singh","doi":"10.15430/JCP.2022.27.1.22","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.22","url":null,"abstract":"Diallyl trisulfide (DATS) was shown to be a potent inhibitor of luminal-type MCF-7 xenograft growth in vivo. The present study was conducted to determine the preventive effect of DATS administration using an N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor model, which shares molecular resemblance to luminal-type human breast cancers. The DATS administration (50 mg/kg body weight, 5 times/week) was safe, but did not reduce mammary tumor latency, incidence, burden or multiplicity. Therefore, we conducted RNA-seq analysis using mammary tumors from control and DATS-treated rats (n = 3 for each group) to gain insights into lack of mammary tumor prevention by this phytochemical. The gene ontology and the Kyoto encyclopedia of genes and genomes pathway analyses of the RNA-seq data revealed upregulation of genes associated with ribosomes, translation, peptide biosynthetic/metabolic process, and oxidative phosphorylation but downregulation of genes associated with mitogen-activated protein kinases. A total of 33 genes associated with ribosomes were significantly upregulated by DATS treatment, including RPL11 and RPS14. Western blotting confirmed upregulation of RPL11 and neurofascin protein expression in mammary tumors from DATS-treated rats when compared to controls. A statistically significant increase in protein level of c-Jun N-terminal kinase 2 was also observed in tumors from DATS-treated rats when compared to controls. On the other hand, expression of complex I subunits NDUFV1 or NDUFS1 was not affected by DATS treatment. These results offer potential explanations for ineffectiveness of DATS in the chemically-induced rat mammary tumor model. Inhibitors of the proteins upregulated by DATS may be needed to improve chemopreventive efficacy of this phytochemical.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"22 - 30"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47594385","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}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.58
Xuchi Pan, Kun Xie, Keyu Chen, Ziyu He, Kozue Sakao, D. Hou
6-(Methylsulfinyl) hexyl isothiocyanate (6-MSITC) is an active ingredient present in Wasabi, which is a popular pungent spice used in Japanese cuisine. Our previous studies suggested that the primary antioxidant activity of 6-MSITC may link to other biological activity. This study aimed to clarify how the antioxidant activity of 6-MSITC contributes to preventing overloaded lipid stress in hepatic cell model. HepG2 cells were treated with 6-MSITC at defined concentrations and times in normal medium or in combined fatty acids (CFA) medium, and the targeted proteins were detected by Western blotting. The kinetic data revealed that 6-MSITC activated AMP-activated protein kinase α (AMPKα) and nuclear factor (erythroid-derived 2) like 2 (Nrf2), and then enhanced the protein expression of Forkhead box protein O1 (FOXO1) and Sirtuin1 as well as that of the Nrf2 target proteins, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO-1). Furthermore, lipid metabolic stress was mimicked in HepG2 cells by overloading CFA. 6-MSITC significantly alleviated CFA-induced formation of thiobarbituric acid reactive substances and fat accumulation. Signaling analysis data revealed that 6-MSITC enhanced phosphorylation of AMPKα, upregulated the expression of Nrf2, NQO1, heme oxygenase 1, FOXO1, and Siruin1, and downregulated the expression of PPARα. Taken together, our results suggested that the AMPKα/Nrf2-mediated signaling pathways might be involved in the cytoprotective effects of Wasabi 6-MSITC against metabolic lipid stress.
{"title":"Involvement of AMP-activated Protein Kinase α/Nuclear Factor (Erythroid-derived 2) Like 2-iniatived Signaling Pathway in Cytoprotective Effects of Wasabi 6-(Methylsulfinyl) Hexyl Isothiocyanate","authors":"Xuchi Pan, Kun Xie, Keyu Chen, Ziyu He, Kozue Sakao, D. Hou","doi":"10.15430/JCP.2022.27.1.58","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.58","url":null,"abstract":"6-(Methylsulfinyl) hexyl isothiocyanate (6-MSITC) is an active ingredient present in Wasabi, which is a popular pungent spice used in Japanese cuisine. Our previous studies suggested that the primary antioxidant activity of 6-MSITC may link to other biological activity. This study aimed to clarify how the antioxidant activity of 6-MSITC contributes to preventing overloaded lipid stress in hepatic cell model. HepG2 cells were treated with 6-MSITC at defined concentrations and times in normal medium or in combined fatty acids (CFA) medium, and the targeted proteins were detected by Western blotting. The kinetic data revealed that 6-MSITC activated AMP-activated protein kinase α (AMPKα) and nuclear factor (erythroid-derived 2) like 2 (Nrf2), and then enhanced the protein expression of Forkhead box protein O1 (FOXO1) and Sirtuin1 as well as that of the Nrf2 target proteins, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO-1). Furthermore, lipid metabolic stress was mimicked in HepG2 cells by overloading CFA. 6-MSITC significantly alleviated CFA-induced formation of thiobarbituric acid reactive substances and fat accumulation. Signaling analysis data revealed that 6-MSITC enhanced phosphorylation of AMPKα, upregulated the expression of Nrf2, NQO1, heme oxygenase 1, FOXO1, and Siruin1, and downregulated the expression of PPARα. Taken together, our results suggested that the AMPKα/Nrf2-mediated signaling pathways might be involved in the cytoprotective effects of Wasabi 6-MSITC against metabolic lipid stress.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"58 - 67"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44555630","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}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.16
R. Issrani, J. Reddy, T. H. E. Dabah, Namdeo Prabhu
A strong and healthy microbiome is responsible for homeostasis between the host and microbiota which is necessary to achieve the normal functioning of the body. Dysbiosis provokes prevalence of pathogenic microbes, leading to alterations in gene expression profiles and metabolic processes. This in turn results in anomalous immune responses of the host. Dysbiosis may be associated with a wide variety of diseases like irritable bowel syndrome, coeliac disease, allergic conditions, bronchitis, asthma, heart diseases and oncogenesis. Presently, the links between oral microbial consortia and their functions, not only in the preservation of homeostasis but also pathogenesis of several malignancies have gained much awareness from the scientific community. The primary intent of this review is to highlight the dynamic role of oral microbiome in oncogenesis and its progression through various mechanisms. A literature search was conducted using multiple databases comprising of PubMed, Scopus, Google Scholar, and Cochrane electronic databases with keywords including microbiome, microbiota, carcinogenesis, tumorigenesis, and immunosuppression. Current and the past literature has pointed out the role of microorganisms in oncogenesis. It may be put forth that both the commensal and pathogenic strains of oral microbiome play an undeniably conspicuous role in carcinogenesis at different body sites.
{"title":"Role of Oral Microbiota in Carcinogenesis: A Short Review","authors":"R. Issrani, J. Reddy, T. H. E. Dabah, Namdeo Prabhu","doi":"10.15430/JCP.2022.27.1.16","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.16","url":null,"abstract":"A strong and healthy microbiome is responsible for homeostasis between the host and microbiota which is necessary to achieve the normal functioning of the body. Dysbiosis provokes prevalence of pathogenic microbes, leading to alterations in gene expression profiles and metabolic processes. This in turn results in anomalous immune responses of the host. Dysbiosis may be associated with a wide variety of diseases like irritable bowel syndrome, coeliac disease, allergic conditions, bronchitis, asthma, heart diseases and oncogenesis. Presently, the links between oral microbial consortia and their functions, not only in the preservation of homeostasis but also pathogenesis of several malignancies have gained much awareness from the scientific community. The primary intent of this review is to highlight the dynamic role of oral microbiome in oncogenesis and its progression through various mechanisms. A literature search was conducted using multiple databases comprising of PubMed, Scopus, Google Scholar, and Cochrane electronic databases with keywords including microbiome, microbiota, carcinogenesis, tumorigenesis, and immunosuppression. Current and the past literature has pointed out the role of microorganisms in oncogenesis. It may be put forth that both the commensal and pathogenic strains of oral microbiome play an undeniably conspicuous role in carcinogenesis at different body sites.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"16 - 21"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45295381","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}
Pub Date : 2022-03-30DOI: 10.15430/jcp.2022.27.1.77
Moon-Young Song, Da-Young Lee, Sang-Yong Park, Seul A. Seo, Jeong-Seung Hwang, S. Heo, Eun-Hee Kim
[This corrects the article on p. 289 in vol. 26, PMID: 35047455.].
[这更正了第26卷第289页的文章，PMID:35047455。]。
{"title":"Steamed Ginger Extract Exerts Anti-inflammatory Effects in Helicobacter pylori-infected Gastric Epithelial Cells through Inhibition of NF-κB","authors":"Moon-Young Song, Da-Young Lee, Sang-Yong Park, Seul A. Seo, Jeong-Seung Hwang, S. Heo, Eun-Hee Kim","doi":"10.15430/jcp.2022.27.1.77","DOIUrl":"https://doi.org/10.15430/jcp.2022.27.1.77","url":null,"abstract":"[This corrects the article on p. 289 in vol. 26, PMID: 35047455.].","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"77 - 77"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44695348","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}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.1
M. Nakayama, Dong Wang, Sau-Yee Kok, H. Oshima, M. Oshima
Comprehensive genome analyses have identified frequently mutated genes in human colorectal cancers (CRC). These include APC, KRAS, SMAD4, TP53, and FBXW7. The biological functions of the respective gene products in cell proliferation and homeostasis have been intensively examined by in vitro experiments. However, how each gene mutation or combinations of specific mutations drive malignant progression of CRC in vivo has not been fully understood. Based on the genomic information, we generated mouse models that carry multiple mutations of CRC driver genes in various combinations, and we performed comprehensive histological analyses to link genetic alteration(s) and tumor phenotypes, including liver metastasis. In this review article, we summarize the phenotypes of the respective genetic models carrying major driver mutations and discuss a possible mechanism of mutations underlying malignant progression.
{"title":"Genetic Alterations and Microenvironment that Drive Malignant Progression of Colorectal Cancer: Lessons from Mouse and Organoid Models","authors":"M. Nakayama, Dong Wang, Sau-Yee Kok, H. Oshima, M. Oshima","doi":"10.15430/JCP.2022.27.1.1","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.1","url":null,"abstract":"Comprehensive genome analyses have identified frequently mutated genes in human colorectal cancers (CRC). These include APC, KRAS, SMAD4, TP53, and FBXW7. The biological functions of the respective gene products in cell proliferation and homeostasis have been intensively examined by in vitro experiments. However, how each gene mutation or combinations of specific mutations drive malignant progression of CRC in vivo has not been fully understood. Based on the genomic information, we generated mouse models that carry multiple mutations of CRC driver genes in various combinations, and we performed comprehensive histological analyses to link genetic alteration(s) and tumor phenotypes, including liver metastasis. In this review article, we summarize the phenotypes of the respective genetic models carrying major driver mutations and discuss a possible mechanism of mutations underlying malignant progression.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"1 - 6"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42678694","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}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.7
A. Jagadeesh, Xizhu Fang, S. Kim, Yanymee N Guillen-Quispe, Jie Zheng, Y. Surh, Su-jung Kim
Heme oxygenase-1 (HO-1) is a critical stress-responsive enzyme that has antioxidant and anti-inflammatory functions. HO-1 catalyzes heme degradation, which gives rise to the formation of carbon monoxide (CO), biliverdin, and iron. The upregulation of HO-1 under pathological conditions associated with cellular stress represents an important cytoprotective defense mechanism by virtue of the anti-oxidant properties of the bilirubin and the anti-inflammatory effect of the CO produced. The same mechanism is hijacked by premalignant and cancerous cells. In recent years, however, there has been accumulating evidence supporting that the upregulation of HO-1 promotes cancer progression, independently of its catalytic activity. Such non-canonical functions of HO-1 are associated with its interaction with other proteins, particularly transcription factors. HO-1 also undergoes post-translational modifications that influence its stability, functional activity, cellular translocation, etc. HO-1 is normally present in the endoplasmic reticulum, but distinct subcellular localizations, especially in the nucleus, are observed in multiple cancers. The nuclear HO-1 modulates the activation of various transcription factors, which does not appear to be mediated by carbon monoxide and iron. This commentary summarizes the non-canonical functions of HO-1 in the context of cancer growth and progression and underlying regulatory mechanisms.
{"title":"Non-canonical vs. Canonical Functions of Heme Oxygenase-1 in Cancer","authors":"A. Jagadeesh, Xizhu Fang, S. Kim, Yanymee N Guillen-Quispe, Jie Zheng, Y. Surh, Su-jung Kim","doi":"10.15430/JCP.2022.27.1.7","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.7","url":null,"abstract":"Heme oxygenase-1 (HO-1) is a critical stress-responsive enzyme that has antioxidant and anti-inflammatory functions. HO-1 catalyzes heme degradation, which gives rise to the formation of carbon monoxide (CO), biliverdin, and iron. The upregulation of HO-1 under pathological conditions associated with cellular stress represents an important cytoprotective defense mechanism by virtue of the anti-oxidant properties of the bilirubin and the anti-inflammatory effect of the CO produced. The same mechanism is hijacked by premalignant and cancerous cells. In recent years, however, there has been accumulating evidence supporting that the upregulation of HO-1 promotes cancer progression, independently of its catalytic activity. Such non-canonical functions of HO-1 are associated with its interaction with other proteins, particularly transcription factors. HO-1 also undergoes post-translational modifications that influence its stability, functional activity, cellular translocation, etc. HO-1 is normally present in the endoplasmic reticulum, but distinct subcellular localizations, especially in the nucleus, are observed in multiple cancers. The nuclear HO-1 modulates the activation of various transcription factors, which does not appear to be mediated by carbon monoxide and iron. This commentary summarizes the non-canonical functions of HO-1 in the context of cancer growth and progression and underlying regulatory mechanisms.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"7 - 15"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46314756","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}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.31
Qinglong Liu, Xiaojing Li, Hao Zhang, Haitao Li
Mannose has recently drawn extensive attention for its substantial anti-cancer activities, but the underlying mechanism remains largely unclear. The aim of this study was to investigate the effects of mannose on experimental colitis-associated colorectal tumorigenesis and underlying mechanisms. Data clearly showed that at plasma concentrations achieved after oral administration, mannose slightly affected malignancy of tumor cells or tumor promoter-induced transformation of pre-neoplastic cells, but substantially suppressed manifestation of the M2-like phenotype of tumor-associated macrophages (TAMs) in a cancer cell and macrophage co-culture model. Mechanistically, mannose might greatly impair the production of tumor cell-derived lactate which has a critical role in the functional polarization of TAMs. Importantly, oral administration of mannose protected mice against colitis-associated colorectal tumorigenesis by normalizing TAM polarization. Collectively, these findings highlight the importance of TAMs in colorectal tumorigenesis, and provide a rationale for introducing mannose supplementation to patients suffering from inflammatory bowel diseases.
{"title":"Mannose Attenuates Colitis-Associated Colorectal Tumorigenesis by Targeting Tumor-Associated Macrophages","authors":"Qinglong Liu, Xiaojing Li, Hao Zhang, Haitao Li","doi":"10.15430/JCP.2022.27.1.31","DOIUrl":"https://doi.org/10.15430/JCP.2022.27.1.31","url":null,"abstract":"Mannose has recently drawn extensive attention for its substantial anti-cancer activities, but the underlying mechanism remains largely unclear. The aim of this study was to investigate the effects of mannose on experimental colitis-associated colorectal tumorigenesis and underlying mechanisms. Data clearly showed that at plasma concentrations achieved after oral administration, mannose slightly affected malignancy of tumor cells or tumor promoter-induced transformation of pre-neoplastic cells, but substantially suppressed manifestation of the M2-like phenotype of tumor-associated macrophages (TAMs) in a cancer cell and macrophage co-culture model. Mechanistically, mannose might greatly impair the production of tumor cell-derived lactate which has a critical role in the functional polarization of TAMs. Importantly, oral administration of mannose protected mice against colitis-associated colorectal tumorigenesis by normalizing TAM polarization. Collectively, these findings highlight the importance of TAMs in colorectal tumorigenesis, and provide a rationale for introducing mannose supplementation to patients suffering from inflammatory bowel diseases.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":"27 1","pages":"31 - 41"},"PeriodicalIF":2.5,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46148264","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}
Pub Date : 2022-03-30DOI: 10.15430/JCP.2022.27.1.42
Jong-Su Kang, Xin Yi Zhao, J. Lee, Jeong-Sang Lee, Y. Keum
Chaenomeles sinensis is known to inhibit the development and progression of many age-related diseases, but the underlying molecular mechanisms are largely unclear. In the present study, we observed that the ethanol extract of Chaenomeles sinensis scavenged 2,2’-diphenylpicrylhydrazyl and 2,2’-azinobis diammonium radicals in vitro. The ethanol extract of Chaenomeles sinensis activated antioxidant response element-luciferase activity and induced expression of NRF2 target genes in HaCaT cells. The ethanol extract of Chaenomeles sinensis also suppressed LPS-induced expression of COX-2 and iNOS proteins, and mRNA expression of TNF-α and IL-2 in RAW264.7 cells. Finally, the ethanol extract of Chaenomeles sinensis significantly suppressed testosterone propionate-induced benign prostatic hyperplasia in mice. Together, our study provides the evidence that the ethanol extract of Chaenomeles sinensis inhibits the development of benign prostatic hyperplasia by exhibiting anti-oxidant and anti-inflammatory effects.
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