Furosemide, a Blocker of Na+/K+/2Cl− Cotransporter, Diminishes Proliferation of Poorly Differentiated Human Gastric Cancer Cells by Affecting G0/G1 State
Furosemide, a blocker of Na+/K+/2Cl− cotransporter (NKCC), is often used as a diuretic to improve edema, ascites, and pleural effusion of patients with cancers. The aim of the present study was to investigate whether an NKCC blocker affects cancer cell growth. If so, we would clarify the mechanism o...
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| Veröffentlicht in: | Journal of Physiological Sciences 2006, Vol.56(6), pp.401-406 |
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| creator | Shiozaki, Atsushi Miyazaki, Hiroaki Niisato, Naomi Nakahari, Takashi Iwasaki, Yoshinobu Itoi, Hirosumi Ueda, Yuji Yamagishi, Hisakazu Marunaka, Yoshinori |
| description | Furosemide, a blocker of Na+/K+/2Cl− cotransporter (NKCC), is often used as a diuretic to improve edema, ascites, and pleural effusion of patients with cancers. The aim of the present study was to investigate whether an NKCC blocker affects cancer cell growth. If so, we would clarify the mechanism of this action. We found that poorly differentiated gastric adenocarcinoma cells (MKN45) expressed the mRNA of NKCC1 three times higher than moderately differentiated ones (MKN28) and that the NKCC in MKN45 showed higher activity than that in MKN28. A cell proliferation assay indicates that furosemide significantly inhibited cell growth in MKN45 cells, but not in MKN28 cells. Using flow cytometrical analysis, we found that the exposure to furosemide brought MKN45 cells to spend more time at the G0/G1 phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G1-S phase progression in poorly differentiated gastric adenocarcinoma cells, which show high expression and activity of NKCC, but not in moderately differentiated gastric adenocarcinoma cells with low expression and NKCC activity. |
| doi_str_mv | 10.2170/physiolsci.RP010806 |
| format | Article |
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The aim of the present study was to investigate whether an NKCC blocker affects cancer cell growth. If so, we would clarify the mechanism of this action. We found that poorly differentiated gastric adenocarcinoma cells (MKN45) expressed the mRNA of NKCC1 three times higher than moderately differentiated ones (MKN28) and that the NKCC in MKN45 showed higher activity than that in MKN28. A cell proliferation assay indicates that furosemide significantly inhibited cell growth in MKN45 cells, but not in MKN28 cells. Using flow cytometrical analysis, we found that the exposure to furosemide brought MKN45 cells to spend more time at the G0/G1 phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G1-S phase progression in poorly differentiated gastric adenocarcinoma cells, which show high expression and activity of NKCC, but not in moderately differentiated gastric adenocarcinoma cells with low expression and NKCC activity.</description><identifier>ISSN: 1880-6546</identifier><identifier>EISSN: 1880-6562</identifier><identifier>DOI: 10.2170/physiolsci.RP010806</identifier><identifier>PMID: 17052386</identifier><language>eng</language><publisher>Japan: PHYSIOLOGICAL SOCIETY OF JAPAN</publisher><subject>Adenocarcinoma - pathology ; cell cycle ; Cell Cycle - drug effects ; Cell Differentiation - drug effects ; Cell Line, Tumor ; cell proliferation ; Cell Proliferation - drug effects ; furosemide ; Furosemide - pharmacology ; G1 Phase - drug effects ; gastric cancer cell ; Humans ; Na+/K+/2Cl− cotransporter (NKCC) ; Resting Phase, Cell Cycle - drug effects ; RNA, Messenger - metabolism ; Sodium Potassium Chloride Symporter Inhibitors - pharmacology ; Sodium-Potassium-Chloride Symporters - metabolism ; Stomach Neoplasms - pathology</subject><ispartof>The Journal of Physiological Sciences, 2006, Vol.56(6), pp.401-406</ispartof><rights>2006 by The Physiological Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6846-da198ce1aae37fec9d68228e98cac8ea477c51c000b978dc63761f06ba4964b13</citedby><cites>FETCH-LOGICAL-c6846-da198ce1aae37fec9d68228e98cac8ea477c51c000b978dc63761f06ba4964b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17052386$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shiozaki, Atsushi</creatorcontrib><creatorcontrib>Miyazaki, Hiroaki</creatorcontrib><creatorcontrib>Niisato, Naomi</creatorcontrib><creatorcontrib>Nakahari, Takashi</creatorcontrib><creatorcontrib>Iwasaki, Yoshinobu</creatorcontrib><creatorcontrib>Itoi, Hirosumi</creatorcontrib><creatorcontrib>Ueda, Yuji</creatorcontrib><creatorcontrib>Yamagishi, Hisakazu</creatorcontrib><creatorcontrib>Marunaka, Yoshinori</creatorcontrib><creatorcontrib>Osaka Medical College</creatorcontrib><creatorcontrib>Department of Molecular Cell Physiology</creatorcontrib><creatorcontrib>Division of Digestive Surgery</creatorcontrib><creatorcontrib>Kyoto Prefectural University of Medicine</creatorcontrib><creatorcontrib>Graduate School of Acupuncture and Moxibustion</creatorcontrib><creatorcontrib>Meiji University of Oriental Medicine</creatorcontrib><creatorcontrib>Department of Respiratory Molecular Medicine</creatorcontrib><creatorcontrib>Department of Surgery</creatorcontrib><creatorcontrib>Department of Physiology</creatorcontrib><creatorcontrib>Graduate School of Medical Science</creatorcontrib><title>Furosemide, a Blocker of Na+/K+/2Cl− Cotransporter, Diminishes Proliferation of Poorly Differentiated Human Gastric Cancer Cells by Affecting G0/G1 State</title><title>Journal of Physiological Sciences</title><addtitle>J. Physiol. Sci</addtitle><description>Furosemide, a blocker of Na+/K+/2Cl− cotransporter (NKCC), is often used as a diuretic to improve edema, ascites, and pleural effusion of patients with cancers. The aim of the present study was to investigate whether an NKCC blocker affects cancer cell growth. If so, we would clarify the mechanism of this action. We found that poorly differentiated gastric adenocarcinoma cells (MKN45) expressed the mRNA of NKCC1 three times higher than moderately differentiated ones (MKN28) and that the NKCC in MKN45 showed higher activity than that in MKN28. A cell proliferation assay indicates that furosemide significantly inhibited cell growth in MKN45 cells, but not in MKN28 cells. Using flow cytometrical analysis, we found that the exposure to furosemide brought MKN45 cells to spend more time at the G0/G1 phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G1-S phase progression in poorly differentiated gastric adenocarcinoma cells, which show high expression and activity of NKCC, but not in moderately differentiated gastric adenocarcinoma cells with low expression and NKCC activity.</description><subject>Adenocarcinoma - pathology</subject><subject>cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line, Tumor</subject><subject>cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>furosemide</subject><subject>Furosemide - pharmacology</subject><subject>G1 Phase - drug effects</subject><subject>gastric cancer cell</subject><subject>Humans</subject><subject>Na+/K+/2Cl− cotransporter (NKCC)</subject><subject>Resting Phase, Cell Cycle - drug effects</subject><subject>RNA, Messenger - metabolism</subject><subject>Sodium Potassium Chloride Symporter Inhibitors - pharmacology</subject><subject>Sodium-Potassium-Chloride Symporters - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><issn>1880-6546</issn><issn>1880-6562</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1uEzEUhUcIREvhCZCQJSQ2bZrr-bnjWZaBpIgKIn7WluPxNA4eO9ieRd6ANVvejifBIWmD2Pha198598g3y55TuMxpDdPNahu0M0Hqy08LoMAAH2SnlDGYYIX5w_t7iSfZkxDWACU2OXucnSR5lRcMT7Nfs9G7oAbdqQsiyGvj5DflievJB3E-fX8-zVvz-8dP0rrohQ0b56PyF-SNHrTVYaUCWXhndK-8iNrZnXDhnDfbhPSpq2zUIqqOXI-DsGQuQvRaklZYmca0yphAlltylVgZtb0lc5jOKfkck-hp9qgXJqhnh3qWfZ29_dJeT24-zt-1VzcTiazESSdow6SiQqiiTjZNhyzPmUpNIZkSZV3LikoAWDY16yQWNdIecCnKBsslLc6yV3vfjXffRxUiH3SQKZqwyo2BJzusaY0JfPkfuHajtykbpyUy1hRQQ6KKPSXTzwaver7xehB-yynw3eb4cXP8bnNJ9eLgPS4H1R01h1UlYL4H0quWwjhrtFXHBHKVb1Y7yxwAOUCFf0vOoQS6O5ACNqyoktNs77QOUdyq-1HCRy2N-jdehRz3x87kDpAr4bmyxR-kUcjJ</recordid><startdate>2006</startdate><enddate>2006</enddate><creator>Shiozaki, Atsushi</creator><creator>Miyazaki, Hiroaki</creator><creator>Niisato, Naomi</creator><creator>Nakahari, Takashi</creator><creator>Iwasaki, Yoshinobu</creator><creator>Itoi, Hirosumi</creator><creator>Ueda, Yuji</creator><creator>Yamagishi, Hisakazu</creator><creator>Marunaka, Yoshinori</creator><general>PHYSIOLOGICAL SOCIETY OF JAPAN</general><general>The Physiological Society of Japan</general><general>BioMed Central</general><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>K9.</scope><scope>7X8</scope></search><sort><creationdate>2006</creationdate><title>Furosemide, a Blocker of Na+/K+/2Cl− Cotransporter, Diminishes Proliferation of Poorly Differentiated Human Gastric Cancer Cells by Affecting G0/G1 State</title><author>Shiozaki, Atsushi ; Miyazaki, Hiroaki ; Niisato, Naomi ; Nakahari, Takashi ; Iwasaki, Yoshinobu ; Itoi, Hirosumi ; Ueda, Yuji ; Yamagishi, Hisakazu ; Marunaka, Yoshinori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6846-da198ce1aae37fec9d68228e98cac8ea477c51c000b978dc63761f06ba4964b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenocarcinoma - pathology</topic><topic>cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line, Tumor</topic><topic>cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>furosemide</topic><topic>Furosemide - pharmacology</topic><topic>G1 Phase - drug effects</topic><topic>gastric cancer cell</topic><topic>Humans</topic><topic>Na+/K+/2Cl− cotransporter (NKCC)</topic><topic>Resting Phase, Cell Cycle - drug effects</topic><topic>RNA, Messenger - metabolism</topic><topic>Sodium Potassium Chloride Symporter Inhibitors - pharmacology</topic><topic>Sodium-Potassium-Chloride Symporters - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shiozaki, Atsushi</creatorcontrib><creatorcontrib>Miyazaki, Hiroaki</creatorcontrib><creatorcontrib>Niisato, Naomi</creatorcontrib><creatorcontrib>Nakahari, Takashi</creatorcontrib><creatorcontrib>Iwasaki, Yoshinobu</creatorcontrib><creatorcontrib>Itoi, Hirosumi</creatorcontrib><creatorcontrib>Ueda, Yuji</creatorcontrib><creatorcontrib>Yamagishi, Hisakazu</creatorcontrib><creatorcontrib>Marunaka, Yoshinori</creatorcontrib><creatorcontrib>Osaka Medical College</creatorcontrib><creatorcontrib>Department of Molecular Cell Physiology</creatorcontrib><creatorcontrib>Division of Digestive Surgery</creatorcontrib><creatorcontrib>Kyoto Prefectural University of Medicine</creatorcontrib><creatorcontrib>Graduate School of Acupuncture and Moxibustion</creatorcontrib><creatorcontrib>Meiji University of Oriental Medicine</creatorcontrib><creatorcontrib>Department of Respiratory Molecular Medicine</creatorcontrib><creatorcontrib>Department of Surgery</creatorcontrib><creatorcontrib>Department of Physiology</creatorcontrib><creatorcontrib>Graduate School of Medical Science</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Physiological Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shiozaki, Atsushi</au><au>Miyazaki, Hiroaki</au><au>Niisato, Naomi</au><au>Nakahari, Takashi</au><au>Iwasaki, Yoshinobu</au><au>Itoi, Hirosumi</au><au>Ueda, Yuji</au><au>Yamagishi, Hisakazu</au><au>Marunaka, Yoshinori</au><aucorp>Osaka Medical College</aucorp><aucorp>Department of Molecular Cell Physiology</aucorp><aucorp>Division of Digestive Surgery</aucorp><aucorp>Kyoto Prefectural University of Medicine</aucorp><aucorp>Graduate School of Acupuncture and Moxibustion</aucorp><aucorp>Meiji University of Oriental Medicine</aucorp><aucorp>Department of Respiratory Molecular Medicine</aucorp><aucorp>Department of Surgery</aucorp><aucorp>Department of Physiology</aucorp><aucorp>Graduate School of Medical Science</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Furosemide, a Blocker of Na+/K+/2Cl− Cotransporter, Diminishes Proliferation of Poorly Differentiated Human Gastric Cancer Cells by Affecting G0/G1 State</atitle><jtitle>Journal of Physiological Sciences</jtitle><addtitle>J. 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Using flow cytometrical analysis, we found that the exposure to furosemide brought MKN45 cells to spend more time at the G0/G1 phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G1-S phase progression in poorly differentiated gastric adenocarcinoma cells, which show high expression and activity of NKCC, but not in moderately differentiated gastric adenocarcinoma cells with low expression and NKCC activity.</abstract><cop>Japan</cop><pub>PHYSIOLOGICAL SOCIETY OF JAPAN</pub><pmid>17052386</pmid><doi>10.2170/physiolsci.RP010806</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adenocarcinoma - pathology cell cycle Cell Cycle - drug effects Cell Differentiation - drug effects Cell Line, Tumor cell proliferation Cell Proliferation - drug effects furosemide Furosemide - pharmacology G1 Phase - drug effects gastric cancer cell Humans Na+/K+/2Cl− cotransporter (NKCC) Resting Phase, Cell Cycle - drug effects RNA, Messenger - metabolism Sodium Potassium Chloride Symporter Inhibitors - pharmacology Sodium-Potassium-Chloride Symporters - metabolism Stomach Neoplasms - pathology |
| title | Furosemide, a Blocker of Na+/K+/2Cl− Cotransporter, Diminishes Proliferation of Poorly Differentiated Human Gastric Cancer Cells by Affecting G0/G1 State |
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