Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences
Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy- β -di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3 H )one (M 1 G) and of expression of the en...
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| Veröffentlicht in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2005-01, Vol.14 (1), p.120-125 |
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| creator | GARCEA, Giuseppe BERRY, David P JONES, Donald J. L SINGH, Raj DENNISON, Ashley R FARMER, Peter B SHARMA, Ricky A STEWARD, William P GESCHER, Andreas J |
| description | Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal
cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy- β -di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3 H )one (M 1 G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels
of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M 1 G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days.
Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after
the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected
and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M 1 G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations
of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace
levels of curcumin were found in the peripheral circulation. M 1 G levels were 2.5-fold higher in malignant tissue as compared with normal tissue ( P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M 1 G levels from 4.8 ± 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 ± 1.8 adducts per 107 nucleotides ( P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest
that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution
of curcumin outside the gut. |
| doi_str_mv | 10.1158/1055-9965.120.14.1 |
| format | Article |
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cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy- β -di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3 H )one (M 1 G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels
of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M 1 G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days.
Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after
the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected
and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M 1 G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations
of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace
levels of curcumin were found in the peripheral circulation. M 1 G levels were 2.5-fold higher in malignant tissue as compared with normal tissue ( P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M 1 G levels from 4.8 ± 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 ± 1.8 adducts per 107 nucleotides ( P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest
that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution
of curcumin outside the gut.</description><identifier>ISSN: 1055-9965</identifier><identifier>EISSN: 1538-7755</identifier><identifier>DOI: 10.1158/1055-9965.120.14.1</identifier><identifier>PMID: 15668484</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Administration, Oral ; Aged ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacokinetics ; Biological and medical sciences ; Biomarkers - metabolism ; Biopsy ; Blotting, Western ; Chemoprevention ; Chromatography, High Pressure Liquid ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; curcumin ; Curcumin - administration & dosage ; Curcumin - pharmacokinetics ; Cyclooxygenase 2 ; DNA Adducts - metabolism ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Male ; Mass Spectrometry ; Medical sciences ; Membrane Proteins ; Middle Aged ; pharmacodynamics ; Prostaglandin-Endoperoxide Synthases - metabolism ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors</subject><ispartof>Cancer epidemiology, biomarkers & prevention, 2005-01, Vol.14 (1), p.120-125</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-ffe744e3b35b90cd296b29eeec3826ef424d5d848b74f6354bc52ffce979875f3</citedby><cites>FETCH-LOGICAL-c407t-ffe744e3b35b90cd296b29eeec3826ef424d5d848b74f6354bc52ffce979875f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3358,4026,27930,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16438811$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15668484$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GARCEA, Giuseppe</creatorcontrib><creatorcontrib>BERRY, David P</creatorcontrib><creatorcontrib>JONES, Donald J. L</creatorcontrib><creatorcontrib>SINGH, Raj</creatorcontrib><creatorcontrib>DENNISON, Ashley R</creatorcontrib><creatorcontrib>FARMER, Peter B</creatorcontrib><creatorcontrib>SHARMA, Ricky A</creatorcontrib><creatorcontrib>STEWARD, William P</creatorcontrib><creatorcontrib>GESCHER, Andreas J</creatorcontrib><title>Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences</title><title>Cancer epidemiology, biomarkers & prevention</title><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><description>Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal
cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy- β -di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3 H )one (M 1 G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels
of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M 1 G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days.
Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after
the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected
and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M 1 G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations
of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace
levels of curcumin were found in the peripheral circulation. M 1 G levels were 2.5-fold higher in malignant tissue as compared with normal tissue ( P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M 1 G levels from 4.8 ± 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 ± 1.8 adducts per 107 nucleotides ( P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest
that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution
of curcumin outside the gut.</description><subject>Administration, Oral</subject><subject>Aged</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Biopsy</subject><subject>Blotting, Western</subject><subject>Chemoprevention</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>curcumin</subject><subject>Curcumin - administration & dosage</subject><subject>Curcumin - pharmacokinetics</subject><subject>Cyclooxygenase 2</subject><subject>DNA Adducts - metabolism</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Membrane Proteins</subject><subject>Middle Aged</subject><subject>pharmacodynamics</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><issn>1055-9965</issn><issn>1538-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc1u3CAUhVHVqknTvkAXFZu2K0-MDcbubmT1J9JIzSJdI4wvMZUxU66daB6o7xk8M21WXC4f58A9hLxn-YYxUV-zXIisaSqxYUVq8Q17QS6ZKOtMSiFepvofcEHeIP7O81w2QrwmF0xUVc1rfkn-tmHCxe9nFyYaLJ0HoLfLrGf3ALQdwId9hAeYjvvtfSpou0SzeDfR7kBbPRmI9Dbx6Qi_0C0iIPqVS2r_0V3SGJGmajVowxgimHnxVE_92nJJY9DRaxP6w6S9M3R9GPxZIBngW_LK6hHh3Xm9Ir--fb1rf2S7n99v2u0uMzyXc2YtSM6h7ErRNbnpi6bqigYATFkXFVhe8F706eOd5LYqBe-MKKw10MimlsKWV-TTSXcfQ7LGWXmHBsZRTxAWVJUsZcVLmcDiBJoYECNYtY_O63hQLFdrOGqdvVpnr1I4inHF0qUPZ_Wl89A_XzmnkYCPZ0Cj0aONaboOn7lkXddsFfp84gZ3Pzy6CMocc4iAoKMZjnarb_kEWT-pMw</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>GARCEA, Giuseppe</creator><creator>BERRY, David P</creator><creator>JONES, Donald J. 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Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Membrane Proteins</topic><topic>Middle Aged</topic><topic>pharmacodynamics</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GARCEA, Giuseppe</creatorcontrib><creatorcontrib>BERRY, David P</creatorcontrib><creatorcontrib>JONES, Donald J. L</creatorcontrib><creatorcontrib>SINGH, Raj</creatorcontrib><creatorcontrib>DENNISON, Ashley R</creatorcontrib><creatorcontrib>FARMER, Peter B</creatorcontrib><creatorcontrib>SHARMA, Ricky A</creatorcontrib><creatorcontrib>STEWARD, William P</creatorcontrib><creatorcontrib>GESCHER, Andreas J</creatorcontrib><collection>Pascal-Francis</collection><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>Cancer epidemiology, biomarkers & prevention</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GARCEA, Giuseppe</au><au>BERRY, David P</au><au>JONES, Donald J. L</au><au>SINGH, Raj</au><au>DENNISON, Ashley R</au><au>FARMER, Peter B</au><au>SHARMA, Ricky A</au><au>STEWARD, William P</au><au>GESCHER, Andreas J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences</atitle><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><date>2005-01-01</date><risdate>2005</risdate><volume>14</volume><issue>1</issue><spage>120</spage><epage>125</epage><pages>120-125</pages><issn>1055-9965</issn><eissn>1538-7755</eissn><abstract>Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal
cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy- β -di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3 H )one (M 1 G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels
of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M 1 G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days.
Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after
the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected
and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M 1 G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations
of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace
levels of curcumin were found in the peripheral circulation. M 1 G levels were 2.5-fold higher in malignant tissue as compared with normal tissue ( P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M 1 G levels from 4.8 ± 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 ± 1.8 adducts per 107 nucleotides ( P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest
that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution
of curcumin outside the gut.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15668484</pmid><doi>10.1158/1055-9965.120.14.1</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer epidemiology, biomarkers & prevention, 2005-01, Vol.14 (1), p.120-125 |
| issn | 1055-9965 1538-7755 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Administration, Oral Aged Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacokinetics Biological and medical sciences Biomarkers - metabolism Biopsy Blotting, Western Chemoprevention Chromatography, High Pressure Liquid Colorectal Neoplasms - drug therapy Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology curcumin Curcumin - administration & dosage Curcumin - pharmacokinetics Cyclooxygenase 2 DNA Adducts - metabolism Female Gastroenterology. Liver. Pancreas. Abdomen Humans Male Mass Spectrometry Medical sciences Membrane Proteins Middle Aged pharmacodynamics Prostaglandin-Endoperoxide Synthases - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
| title | Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences |
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