Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9+ cancer stem cells in ulcerative colitis-related cancer
Summary Background and objective Sulfasalazine reduces the risk of ulcerative colitis (UC)-related cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells by inhibiting the glutamate–cystine transporter, which is closely associated with the cancer stem cell surf...
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| Veröffentlicht in: | Clinics and research in hepatology and gastroenterology 2016-09, Vol.40 (4), p.487-493 |
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| creator | Seishima, Ryo Okabayashi, Koji Nagano, Osamu Hasegawa, Hirotoshi Tsuruta, Masashi Shimoda, Masayuki Kameyama, Kaori Saya, Hideyuki Kitagawa, Yuko |
| description | Summary Background and objective Sulfasalazine reduces the risk of ulcerative colitis (UC)-related cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells by inhibiting the glutamate–cystine transporter, which is closely associated with the cancer stem cell surface marker CD44v9. This study aimed to quantify the effects of sulfasalazine on CD44v9 expression and pathological factors in colorectal cancers (CRCs) arising from UC. Methods Twenty-six patients with UC-related cancer were classified into groups according to the length of sulfasalazine treatment as follows: (1) long-term (LT) (≥ 5 years) and (2) short-term (ST) ( |
| doi_str_mv | 10.1016/j.clinre.2015.11.007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1822115520</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S2210740115002880</els_id><sourcerecordid>1822115520</sourcerecordid><originalsourceid>FETCH-LOGICAL-c428t-3b970133adeaf00f7e2fc67d47e10be9c93fd560d2d7bc6e4e80b07c9333e0b13</originalsourceid><addsrcrecordid>eNptkc1u1DAUhS0EolXbN0DISySa9F7nx8kGCU35kyqxKEjsLMe56XjwJIPtDGqfoo-Mwwxd4Y2tq3OO7fMx9gohR8D6apMbZ0dPuQCscsQcQD5jp0IgZLLEH8-fzoAn7CKEDaRVVtBIfMlORC1l1bR4yh5vZzfooJ1-sCNdcs3jmrze0Ryt4fqOxsiHyfPZmTSOdk_cTM5GGy65Hde2szEsFn7np99xzaeBr67Lct--5UaPycNDpC035FxIhv_kZJ6cjtQf9efsxaBdoIvjfsa-f_zwbfU5u_n66cvq_U1mStHErOhaCVgUuic9AAySxGBq2ZeSEDpqTVsMfVVDL3rZmZpKaqADmcZFQdBhccbeHHJ3fvo1U4hqa8PyTD3SNAeFTSoQq0pAkpYHqfFTCJ4GtfN2q_29QlALDrVRBxxqwaEQVcKRbK-PN8zdlvon07_yk-DdQUDpn3tL_m-KNdr9pHsKm2n2Y6pAoQpCgbpdiC5AsQIQTQPFH5sqnv8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1822115520</pqid></control><display><type>article</type><title>Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9+ cancer stem cells in ulcerative colitis-related cancer</title><source>Elsevier ScienceDirect Journals Complete - AutoHoldings</source><source>MEDLINE</source><creator>Seishima, Ryo ; Okabayashi, Koji ; Nagano, Osamu ; Hasegawa, Hirotoshi ; Tsuruta, Masashi ; Shimoda, Masayuki ; Kameyama, Kaori ; Saya, Hideyuki ; Kitagawa, Yuko</creator><creatorcontrib>Seishima, Ryo ; Okabayashi, Koji ; Nagano, Osamu ; Hasegawa, Hirotoshi ; Tsuruta, Masashi ; Shimoda, Masayuki ; Kameyama, Kaori ; Saya, Hideyuki ; Kitagawa, Yuko</creatorcontrib><description>Summary Background and objective Sulfasalazine reduces the risk of ulcerative colitis (UC)-related cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells by inhibiting the glutamate–cystine transporter, which is closely associated with the cancer stem cell surface marker CD44v9. This study aimed to quantify the effects of sulfasalazine on CD44v9 expression and pathological factors in colorectal cancers (CRCs) arising from UC. Methods Twenty-six patients with UC-related cancer were classified into groups according to the length of sulfasalazine treatment as follows: (1) long-term (LT) (≥ 5 years) and (2) short-term (ST) (< 5 years). Using immunohistochemistry, we compared CD44v9 and Ki-67 expression and pathological characteristics of each group's tumors. In vitro assay was performed to investigate the effect of sulfasalazine on epithelial differentiation and proliferation of CD44+ cancer cells. Results Immunohistochemical analysis revealed that CD44v9 expression tended to be lower in the LT group (LT:ST = 15.4%:46.2%, P = 0.20), and Ki-67/CD44v9 double-stained cells were significantly lower in the LT group (LT:ST = 0%:6.9%, P = 0.01). Pathologically, the frequency of well-differentiated adenocarcinomas was higher in the LT group (LT:ST = 84.6%:38.5%, P = 0.04). In vitro assay revealed that sulfasalazine promoted the expression of epithelial differentiation markers (E-cadherin and CDX2) and inhibited the proliferation of CD44+ cancer cells. Conclusions Long-term sulfasalazine administration reduced proliferative CD44v9+ cells and increased the degree of differentiation of adenocarcinomas. These findings indicate the importance of CD44v9+ cells in UC-related cancer progression and suggest that sulfasalazine may serve as a novel therapeutic agent that targets CD44v9+ cells.</description><identifier>ISSN: 2210-7401</identifier><identifier>EISSN: 2210-741X</identifier><identifier>DOI: 10.1016/j.clinre.2015.11.007</identifier><identifier>PMID: 26775891</identifier><language>eng</language><publisher>France</publisher><subject>Adenocarcinoma - pathology ; Adult ; Aged ; Cadherins - metabolism ; CDX2 Transcription Factor - metabolism ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; Colitis, Ulcerative - drug therapy ; Colorectal Neoplasms - pathology ; Down-Regulation ; Female ; Gastroenterology and Hepatology ; Gastrointestinal Agents - pharmacology ; Humans ; Hyaluronan Receptors - genetics ; Hyaluronan Receptors - metabolism ; Immunohistochemistry ; Internal Medicine ; Ki-67 Antigen - metabolism ; Male ; Middle Aged ; Neoplastic Stem Cells - drug effects ; Retrospective Studies ; RNA, Messenger - metabolism ; Sulfasalazine - pharmacology</subject><ispartof>Clinics and research in hepatology and gastroenterology, 2016-09, Vol.40 (4), p.487-493</ispartof><rights>Elsevier Masson SAS</rights><rights>Copyright © 2015 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-3b970133adeaf00f7e2fc67d47e10be9c93fd560d2d7bc6e4e80b07c9333e0b13</citedby><cites>FETCH-LOGICAL-c428t-3b970133adeaf00f7e2fc67d47e10be9c93fd560d2d7bc6e4e80b07c9333e0b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26775891$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seishima, Ryo</creatorcontrib><creatorcontrib>Okabayashi, Koji</creatorcontrib><creatorcontrib>Nagano, Osamu</creatorcontrib><creatorcontrib>Hasegawa, Hirotoshi</creatorcontrib><creatorcontrib>Tsuruta, Masashi</creatorcontrib><creatorcontrib>Shimoda, Masayuki</creatorcontrib><creatorcontrib>Kameyama, Kaori</creatorcontrib><creatorcontrib>Saya, Hideyuki</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><title>Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9+ cancer stem cells in ulcerative colitis-related cancer</title><title>Clinics and research in hepatology and gastroenterology</title><addtitle>Clin Res Hepatol Gastroenterol</addtitle><description>Summary Background and objective Sulfasalazine reduces the risk of ulcerative colitis (UC)-related cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells by inhibiting the glutamate–cystine transporter, which is closely associated with the cancer stem cell surface marker CD44v9. This study aimed to quantify the effects of sulfasalazine on CD44v9 expression and pathological factors in colorectal cancers (CRCs) arising from UC. Methods Twenty-six patients with UC-related cancer were classified into groups according to the length of sulfasalazine treatment as follows: (1) long-term (LT) (≥ 5 years) and (2) short-term (ST) (< 5 years). Using immunohistochemistry, we compared CD44v9 and Ki-67 expression and pathological characteristics of each group's tumors. In vitro assay was performed to investigate the effect of sulfasalazine on epithelial differentiation and proliferation of CD44+ cancer cells. Results Immunohistochemical analysis revealed that CD44v9 expression tended to be lower in the LT group (LT:ST = 15.4%:46.2%, P = 0.20), and Ki-67/CD44v9 double-stained cells were significantly lower in the LT group (LT:ST = 0%:6.9%, P = 0.01). Pathologically, the frequency of well-differentiated adenocarcinomas was higher in the LT group (LT:ST = 84.6%:38.5%, P = 0.04). In vitro assay revealed that sulfasalazine promoted the expression of epithelial differentiation markers (E-cadherin and CDX2) and inhibited the proliferation of CD44+ cancer cells. Conclusions Long-term sulfasalazine administration reduced proliferative CD44v9+ cells and increased the degree of differentiation of adenocarcinomas. These findings indicate the importance of CD44v9+ cells in UC-related cancer progression and suggest that sulfasalazine may serve as a novel therapeutic agent that targets CD44v9+ cells.</description><subject>Adenocarcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Cadherins - metabolism</subject><subject>CDX2 Transcription Factor - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Gastroenterology and Hepatology</subject><subject>Gastrointestinal Agents - pharmacology</subject><subject>Humans</subject><subject>Hyaluronan Receptors - genetics</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Immunohistochemistry</subject><subject>Internal Medicine</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Retrospective Studies</subject><subject>RNA, Messenger - metabolism</subject><subject>Sulfasalazine - pharmacology</subject><issn>2210-7401</issn><issn>2210-741X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1u1DAUhS0EolXbN0DISySa9F7nx8kGCU35kyqxKEjsLMe56XjwJIPtDGqfoo-Mwwxd4Y2tq3OO7fMx9gohR8D6apMbZ0dPuQCscsQcQD5jp0IgZLLEH8-fzoAn7CKEDaRVVtBIfMlORC1l1bR4yh5vZzfooJ1-sCNdcs3jmrze0Ryt4fqOxsiHyfPZmTSOdk_cTM5GGy65Hde2szEsFn7np99xzaeBr67Lct--5UaPycNDpC035FxIhv_kZJ6cjtQf9efsxaBdoIvjfsa-f_zwbfU5u_n66cvq_U1mStHErOhaCVgUuic9AAySxGBq2ZeSEDpqTVsMfVVDL3rZmZpKaqADmcZFQdBhccbeHHJ3fvo1U4hqa8PyTD3SNAeFTSoQq0pAkpYHqfFTCJ4GtfN2q_29QlALDrVRBxxqwaEQVcKRbK-PN8zdlvon07_yk-DdQUDpn3tL_m-KNdr9pHsKm2n2Y6pAoQpCgbpdiC5AsQIQTQPFH5sqnv8</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Seishima, Ryo</creator><creator>Okabayashi, Koji</creator><creator>Nagano, Osamu</creator><creator>Hasegawa, Hirotoshi</creator><creator>Tsuruta, Masashi</creator><creator>Shimoda, Masayuki</creator><creator>Kameyama, Kaori</creator><creator>Saya, Hideyuki</creator><creator>Kitagawa, Yuko</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160901</creationdate><title>Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9+ cancer stem cells in ulcerative colitis-related cancer</title><author>Seishima, Ryo ; Okabayashi, Koji ; Nagano, Osamu ; Hasegawa, Hirotoshi ; Tsuruta, Masashi ; Shimoda, Masayuki ; Kameyama, Kaori ; Saya, Hideyuki ; Kitagawa, Yuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-3b970133adeaf00f7e2fc67d47e10be9c93fd560d2d7bc6e4e80b07c9333e0b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma - pathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Cadherins - metabolism</topic><topic>CDX2 Transcription Factor - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Gastroenterology and Hepatology</topic><topic>Gastrointestinal Agents - pharmacology</topic><topic>Humans</topic><topic>Hyaluronan Receptors - genetics</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Immunohistochemistry</topic><topic>Internal Medicine</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Retrospective Studies</topic><topic>RNA, Messenger - metabolism</topic><topic>Sulfasalazine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seishima, Ryo</creatorcontrib><creatorcontrib>Okabayashi, Koji</creatorcontrib><creatorcontrib>Nagano, Osamu</creatorcontrib><creatorcontrib>Hasegawa, Hirotoshi</creatorcontrib><creatorcontrib>Tsuruta, Masashi</creatorcontrib><creatorcontrib>Shimoda, Masayuki</creatorcontrib><creatorcontrib>Kameyama, Kaori</creatorcontrib><creatorcontrib>Saya, Hideyuki</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinics and research in hepatology and gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seishima, Ryo</au><au>Okabayashi, Koji</au><au>Nagano, Osamu</au><au>Hasegawa, Hirotoshi</au><au>Tsuruta, Masashi</au><au>Shimoda, Masayuki</au><au>Kameyama, Kaori</au><au>Saya, Hideyuki</au><au>Kitagawa, Yuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9+ cancer stem cells in ulcerative colitis-related cancer</atitle><jtitle>Clinics and research in hepatology and gastroenterology</jtitle><addtitle>Clin Res Hepatol Gastroenterol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>40</volume><issue>4</issue><spage>487</spage><epage>493</epage><pages>487-493</pages><issn>2210-7401</issn><eissn>2210-741X</eissn><abstract>Summary Background and objective Sulfasalazine reduces the risk of ulcerative colitis (UC)-related cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells by inhibiting the glutamate–cystine transporter, which is closely associated with the cancer stem cell surface marker CD44v9. This study aimed to quantify the effects of sulfasalazine on CD44v9 expression and pathological factors in colorectal cancers (CRCs) arising from UC. Methods Twenty-six patients with UC-related cancer were classified into groups according to the length of sulfasalazine treatment as follows: (1) long-term (LT) (≥ 5 years) and (2) short-term (ST) (< 5 years). Using immunohistochemistry, we compared CD44v9 and Ki-67 expression and pathological characteristics of each group's tumors. In vitro assay was performed to investigate the effect of sulfasalazine on epithelial differentiation and proliferation of CD44+ cancer cells. Results Immunohistochemical analysis revealed that CD44v9 expression tended to be lower in the LT group (LT:ST = 15.4%:46.2%, P = 0.20), and Ki-67/CD44v9 double-stained cells were significantly lower in the LT group (LT:ST = 0%:6.9%, P = 0.01). Pathologically, the frequency of well-differentiated adenocarcinomas was higher in the LT group (LT:ST = 84.6%:38.5%, P = 0.04). In vitro assay revealed that sulfasalazine promoted the expression of epithelial differentiation markers (E-cadherin and CDX2) and inhibited the proliferation of CD44+ cancer cells. Conclusions Long-term sulfasalazine administration reduced proliferative CD44v9+ cells and increased the degree of differentiation of adenocarcinomas. These findings indicate the importance of CD44v9+ cells in UC-related cancer progression and suggest that sulfasalazine may serve as a novel therapeutic agent that targets CD44v9+ cells.</abstract><cop>France</cop><pmid>26775891</pmid><doi>10.1016/j.clinre.2015.11.007</doi><tpages>7</tpages></addata></record> |
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| subjects | Adenocarcinoma - pathology Adult Aged Cadherins - metabolism CDX2 Transcription Factor - metabolism Cell Differentiation - drug effects Cell Proliferation - drug effects Colitis, Ulcerative - drug therapy Colorectal Neoplasms - pathology Down-Regulation Female Gastroenterology and Hepatology Gastrointestinal Agents - pharmacology Humans Hyaluronan Receptors - genetics Hyaluronan Receptors - metabolism Immunohistochemistry Internal Medicine Ki-67 Antigen - metabolism Male Middle Aged Neoplastic Stem Cells - drug effects Retrospective Studies RNA, Messenger - metabolism Sulfasalazine - pharmacology |
| title | Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9+ cancer stem cells in ulcerative colitis-related cancer |
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