Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells
The peripheral benzodiazepine receptor (PBR) has been implicated in growth control of various tumour models. Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorect...
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| Veröffentlicht in: | British journal of cancer 2001-11, Vol.85 (11), p.1771-1780 |
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| container_title | British journal of cancer |
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| creator | Maaser, K Höpfner, M Jansen, A Weisinger, G Gavish, M Kozikowski, A P Weizman, A Carayon, P Riecken, E-O Zeitz, M Scherübl, H |
| description | The peripheral benzodiazepine receptor (PBR) has been implicated in growth control of various tumour models. Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorectal cancers and the human colorectal carcinoma cell lines HT29, LS174T, and Colo320 DM we studied the involvement of PBR in the growth control and apoptosis of colorectal cancers. Both mRNA and protein expression of PBR were detected by RT-PCR and flow cytometry. Using confocal laser scanning microscopy and immunohistochemistry the PBR was localized in the mitochondria. The specific PBR ligands FGIN-1-27, PK 11195, or Ro5-4864 inhibited cell proliferation dose-dependently. FGIN-1-27 decreased the mitochondrial membrane potential, which indicates an early event in apoptosis. Furthermore, FGIN-1-27, PK 11195 or Ro5-4864 increased caspase-3 activity. In addition to their apoptosis-inducing effects, PBR ligands induced cell cycle arrest in the G
1
/G
0
-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer. © 2001 Cancer Research Campaign
http://www.bjcancer.com |
| doi_str_mv | 10.1054/bjoc.2001.2181 |
| format | Article |
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1
/G
0
-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer. © 2001 Cancer Research Campaign
http://www.bjcancer.com</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1054/bjoc.2001.2181</identifier><identifier>PMID: 11742501</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adult ; Aged ; Apoptosis ; Apoptosis - drug effects ; Benzodiazepines ; Benzodiazepinones - metabolism ; Benzodiazepinones - pharmacology ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Cancer Research ; Cell cycle ; Cell Cycle - drug effects ; Cell Cycle - physiology ; Cell division ; Cell growth ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - physiopathology ; Dose-Response Relationship, Drug ; Drug Resistance ; Epidemiology ; G1 Phase - drug effects ; G1 Phase - physiology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation, Neoplastic ; Hospitals ; HT29 Cells ; Humans ; Indoleacetic Acids - metabolism ; Indoleacetic Acids - pharmacology ; Intracellular Membranes - drug effects ; Intracellular Membranes - physiology ; Isoquinolines - metabolism ; Isoquinolines - pharmacology ; Ligands ; Localization ; Medical research ; Medical sciences ; Melanoma ; Membrane Potentials - drug effects ; Middle Aged ; Mitochondria - chemistry ; Mitochondria - drug effects ; Mitochondria - physiology ; Molecular Medicine ; Oncology ; Ovaries ; Permeability ; Receptors, GABA-A - genetics ; Receptors, GABA-A - metabolism ; Regular ; regular-article ; Resting Phase, Cell Cycle - drug effects ; Resting Phase, Cell Cycle - physiology ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Steroids ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumor Cells, Cultured - drug effects ; Tumors</subject><ispartof>British journal of cancer, 2001-11, Vol.85 (11), p.1771-1780</ispartof><rights>The Author(s) 2001</rights><rights>2002 INIST-CNRS</rights><rights>(c) 2001 Cancer Research Campaign</rights><rights>Copyright Nature Publishing Group Nov 2001</rights><rights>Copyright © 2001 Cancer Research Campaign 2001 Cancer Research Campaign</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-2cbfdc4279796cb1fca0c191e82863d55d5c9eb91b8419c1e0e5ef3551d9e7a83</citedby><cites>FETCH-LOGICAL-c581t-2cbfdc4279796cb1fca0c191e82863d55d5c9eb91b8419c1e0e5ef3551d9e7a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363981/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363981/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13444139$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11742501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maaser, K</creatorcontrib><creatorcontrib>Höpfner, M</creatorcontrib><creatorcontrib>Jansen, A</creatorcontrib><creatorcontrib>Weisinger, G</creatorcontrib><creatorcontrib>Gavish, M</creatorcontrib><creatorcontrib>Kozikowski, A P</creatorcontrib><creatorcontrib>Weizman, A</creatorcontrib><creatorcontrib>Carayon, P</creatorcontrib><creatorcontrib>Riecken, E-O</creatorcontrib><creatorcontrib>Zeitz, M</creatorcontrib><creatorcontrib>Scherübl, H</creatorcontrib><title>Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>The peripheral benzodiazepine receptor (PBR) has been implicated in growth control of various tumour models. Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorectal cancers and the human colorectal carcinoma cell lines HT29, LS174T, and Colo320 DM we studied the involvement of PBR in the growth control and apoptosis of colorectal cancers. Both mRNA and protein expression of PBR were detected by RT-PCR and flow cytometry. Using confocal laser scanning microscopy and immunohistochemistry the PBR was localized in the mitochondria. The specific PBR ligands FGIN-1-27, PK 11195, or Ro5-4864 inhibited cell proliferation dose-dependently. FGIN-1-27 decreased the mitochondrial membrane potential, which indicates an early event in apoptosis. Furthermore, FGIN-1-27, PK 11195 or Ro5-4864 increased caspase-3 activity. In addition to their apoptosis-inducing effects, PBR ligands induced cell cycle arrest in the G
1
/G
0
-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer. © 2001 Cancer Research Campaign
http://www.bjcancer.com</description><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Benzodiazepines</subject><subject>Benzodiazepinones - metabolism</subject><subject>Benzodiazepinones - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Cancer Research</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Cycle - physiology</subject><subject>Cell division</subject><subject>Cell growth</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - physiopathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>G1 Phase - drug effects</subject><subject>G1 Phase - physiology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hospitals</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Indoleacetic Acids - metabolism</subject><subject>Indoleacetic Acids - pharmacology</subject><subject>Intracellular Membranes - drug effects</subject><subject>Intracellular Membranes - physiology</subject><subject>Isoquinolines - metabolism</subject><subject>Isoquinolines - pharmacology</subject><subject>Ligands</subject><subject>Localization</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Melanoma</subject><subject>Membrane Potentials - drug effects</subject><subject>Middle Aged</subject><subject>Mitochondria - chemistry</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - physiology</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Ovaries</subject><subject>Permeability</subject><subject>Receptors, GABA-A - genetics</subject><subject>Receptors, GABA-A - metabolism</subject><subject>Regular</subject><subject>regular-article</subject><subject>Resting Phase, Cell Cycle - drug effects</subject><subject>Resting Phase, Cell Cycle - physiology</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Steroids</subject><subject>Stomach. 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Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hospitals</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Indoleacetic Acids - metabolism</topic><topic>Indoleacetic Acids - pharmacology</topic><topic>Intracellular Membranes - drug effects</topic><topic>Intracellular Membranes - physiology</topic><topic>Isoquinolines - metabolism</topic><topic>Isoquinolines - pharmacology</topic><topic>Ligands</topic><topic>Localization</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Melanoma</topic><topic>Membrane Potentials - drug effects</topic><topic>Middle Aged</topic><topic>Mitochondria - chemistry</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - physiology</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Ovaries</topic><topic>Permeability</topic><topic>Receptors, GABA-A - genetics</topic><topic>Receptors, GABA-A - metabolism</topic><topic>Regular</topic><topic>regular-article</topic><topic>Resting Phase, Cell Cycle - drug effects</topic><topic>Resting Phase, Cell Cycle - physiology</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Steroids</topic><topic>Stomach. 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Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorectal cancers and the human colorectal carcinoma cell lines HT29, LS174T, and Colo320 DM we studied the involvement of PBR in the growth control and apoptosis of colorectal cancers. Both mRNA and protein expression of PBR were detected by RT-PCR and flow cytometry. Using confocal laser scanning microscopy and immunohistochemistry the PBR was localized in the mitochondria. The specific PBR ligands FGIN-1-27, PK 11195, or Ro5-4864 inhibited cell proliferation dose-dependently. FGIN-1-27 decreased the mitochondrial membrane potential, which indicates an early event in apoptosis. Furthermore, FGIN-1-27, PK 11195 or Ro5-4864 increased caspase-3 activity. In addition to their apoptosis-inducing effects, PBR ligands induced cell cycle arrest in the G
1
/G
0
-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer. © 2001 Cancer Research Campaign
http://www.bjcancer.com</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>11742501</pmid><doi>10.1054/bjoc.2001.2181</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2001-11, Vol.85 (11), p.1771-1780 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2363981 |
| source | MEDLINE; SpringerLink Journals (MCLS); Nature; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult Aged Apoptosis Apoptosis - drug effects Benzodiazepines Benzodiazepinones - metabolism Benzodiazepinones - pharmacology Biological and medical sciences Biomedical and Life Sciences Biomedicine Breast cancer Cancer Research Cell cycle Cell Cycle - drug effects Cell Cycle - physiology Cell division Cell growth Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Colorectal Neoplasms - physiopathology Dose-Response Relationship, Drug Drug Resistance Epidemiology G1 Phase - drug effects G1 Phase - physiology Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation, Neoplastic Hospitals HT29 Cells Humans Indoleacetic Acids - metabolism Indoleacetic Acids - pharmacology Intracellular Membranes - drug effects Intracellular Membranes - physiology Isoquinolines - metabolism Isoquinolines - pharmacology Ligands Localization Medical research Medical sciences Melanoma Membrane Potentials - drug effects Middle Aged Mitochondria - chemistry Mitochondria - drug effects Mitochondria - physiology Molecular Medicine Oncology Ovaries Permeability Receptors, GABA-A - genetics Receptors, GABA-A - metabolism Regular regular-article Resting Phase, Cell Cycle - drug effects Resting Phase, Cell Cycle - physiology RNA, Messenger - genetics RNA, Messenger - metabolism Steroids Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumor Cells, Cultured - drug effects Tumors |
| title | Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells |
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