Black Raspberry Components Inhibit Proliferation, Induce Apoptosis, and Modulate Gene Expression in Rat Esophageal Epithelial Cells
We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two co...
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| Veröffentlicht in: | Nutrition and cancer 2009-01, Vol.61 (6), p.816-826 |
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| creator | Zikri, Nancy N Riedl, Kenneth M Wang, Li-Shu Lechner, John Schwartz, Steven J Stoner, Gary D |
| description | We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for their effects on growth, apoptosis, and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and proapoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells, whereas both anthocyanins downregulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract vs. when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo. |
| doi_str_mv | 10.1080/01635580903285148 |
| format | Article |
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To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for their effects on growth, apoptosis, and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and proapoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells, whereas both anthocyanins downregulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract vs. when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo.</description><identifier>ISSN: 0163-5581</identifier><identifier>EISSN: 1532-7914</identifier><identifier>DOI: 10.1080/01635580903285148</identifier><identifier>PMID: 20155622</identifier><identifier>CODEN: NUCADQ</identifier><language>eng</language><publisher>Philadelphia, PA: Taylor & Francis Group</publisher><subject>animal disease models ; Animals ; Animals, Newborn ; Anthocyanins - analysis ; Anthocyanins - chemistry ; Anthocyanins - pharmacokinetics ; Anthocyanins - pharmacology ; anticarcinogenic activity ; Antineoplastic Agents, Phytogenic - analysis ; Antineoplastic Agents, Phytogenic - chemistry ; Antineoplastic Agents, Phytogenic - pharmacokinetics ; Antineoplastic Agents, Phytogenic - pharmacology ; apoptosis ; Apoptosis - drug effects ; Biological and medical sciences ; carcinogenesis ; Caspases, Effector - genetics ; Caspases, Effector - metabolism ; cell culture ; cell cycle ; Cell Line, Tumor ; cell proliferation ; Cell Proliferation - drug effects ; Cell Transformation, Neoplastic - chemically induced ; chemical constituents of plants ; cyanin ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - metabolism ; dietary exposure ; Dose-Response Relationship, Drug ; dried fruit ; epidemiological studies ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; esophageal neoplasms ; Esophageal Neoplasms - drug therapy ; Esophageal Neoplasms - metabolism ; esophagus ; Feeding. Feeding behavior ; freeze drying ; Fruit - chemistry ; fruit composition ; fruit extracts ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Neoplastic - drug effects ; Glucosides - analysis ; Glucosides - chemistry ; Glucosides - pharmacokinetics ; Glucosides - pharmacology ; Neoplasm Transplantation ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; nutrition-genotype interaction ; nutritional intervention ; Phytotherapy ; Plant Extracts - administration & dosage ; Plant Extracts - chemistry ; Plant Extracts - pharmacology ; Rats ; Rats, Inbred F344 ; Rosaceae - chemistry ; Rubus occidentalis ; small fruits ; Time Factors ; Tumor Burden ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Nutrition and cancer, 2009-01, Vol.61 (6), p.816-826</ispartof><rights>Copyright Taylor & Francis Group, LLC 2009</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-ba470aab5e2a73da9c349d5eb5eb4279d33675196ee55ac151911b0f03e692393</citedby><cites>FETCH-LOGICAL-c553t-ba470aab5e2a73da9c349d5eb5eb4279d33675196ee55ac151911b0f03e692393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/01635580903285148$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/01635580903285148$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>230,309,310,314,776,780,785,786,881,23909,23910,25118,27901,27902,59620,60409</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22308844$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20155622$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zikri, Nancy N</creatorcontrib><creatorcontrib>Riedl, Kenneth M</creatorcontrib><creatorcontrib>Wang, Li-Shu</creatorcontrib><creatorcontrib>Lechner, John</creatorcontrib><creatorcontrib>Schwartz, Steven J</creatorcontrib><creatorcontrib>Stoner, Gary D</creatorcontrib><title>Black Raspberry Components Inhibit Proliferation, Induce Apoptosis, and Modulate Gene Expression in Rat Esophageal Epithelial Cells</title><title>Nutrition and cancer</title><addtitle>Nutr Cancer</addtitle><description>We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for their effects on growth, apoptosis, and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and proapoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells, whereas both anthocyanins downregulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract vs. when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo.</description><subject>animal disease models</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Anthocyanins - analysis</subject><subject>Anthocyanins - chemistry</subject><subject>Anthocyanins - pharmacokinetics</subject><subject>Anthocyanins - pharmacology</subject><subject>anticarcinogenic activity</subject><subject>Antineoplastic Agents, Phytogenic - analysis</subject><subject>Antineoplastic Agents, Phytogenic - chemistry</subject><subject>Antineoplastic Agents, Phytogenic - pharmacokinetics</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>carcinogenesis</subject><subject>Caspases, Effector - genetics</subject><subject>Caspases, Effector - metabolism</subject><subject>cell culture</subject><subject>cell cycle</subject><subject>Cell Line, Tumor</subject><subject>cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Transformation, Neoplastic - chemically induced</subject><subject>chemical constituents of plants</subject><subject>cyanin</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>dietary exposure</subject><subject>Dose-Response Relationship, Drug</subject><subject>dried fruit</subject><subject>epidemiological studies</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>esophageal neoplasms</subject><subject>Esophageal Neoplasms - drug therapy</subject><subject>Esophageal Neoplasms - metabolism</subject><subject>esophagus</subject><subject>Feeding. Feeding behavior</subject><subject>freeze drying</subject><subject>Fruit - chemistry</subject><subject>fruit composition</subject><subject>fruit extracts</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Glucosides - analysis</subject><subject>Glucosides - chemistry</subject><subject>Glucosides - pharmacokinetics</subject><subject>Glucosides - pharmacology</subject><subject>Neoplasm Transplantation</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>nutrition-genotype interaction</subject><subject>nutritional intervention</subject><subject>Phytotherapy</subject><subject>Plant Extracts - administration & dosage</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Extracts - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rosaceae - chemistry</subject><subject>Rubus occidentalis</subject><subject>small fruits</subject><subject>Time Factors</subject><subject>Tumor Burden</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>0163-5581</issn><issn>1532-7914</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vFDEMhiMEokvhB3CBXLh12mQymQ8JVSqrpa3UCgT0HHlmPLuBbBIlWeie-eOk2raAKsEplv28r2ObkJecHXLWsiPGayFlyzomylbyqn1EZlyKsmg6Xj0ms5t6kQG-R57F-JUx1nDRPiV7JeNS1mU5Iz_fGRi-0U8QfY8hbOncrb2zaFOk53ale53ox-CMnjBA0s4e5PS4GZCeeOeTizoeULAjvXTjxkBCeooW6eLaB4wx81Tb7J7oIjq_giWCoQuv0wqNzuEcjYnPyZMJTMQXt-8-uXq_-DI_Ky4-nJ7PTy6KQUqRih6qhgH0EktoxAjdIKpulJgTfVU23ShE3Uje1YhSwsBzyHnPJiaw7krRiX1yvPP1m36N45CHDGCUD3oNYascaPV3xeqVWrrvSuR1sbbJBnxnMAQXY8DpXsuZurmIenCRrHn1Z9N7xd0JMvDmFoA4gJkC2EHH31wpWNtWVeaaHaft5MIafrhgRpVga1y4Ez1or9J1ysq3_1WKf03weiefwClYhkxffc7fz1tpeCfyan8ByYnEVQ</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Zikri, Nancy N</creator><creator>Riedl, Kenneth M</creator><creator>Wang, Li-Shu</creator><creator>Lechner, John</creator><creator>Schwartz, Steven J</creator><creator>Stoner, Gary D</creator><general>Taylor & Francis Group</general><general>Taylor& Francis</general><scope>FBQ</scope><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>20090101</creationdate><title>Black Raspberry Components Inhibit Proliferation, Induce Apoptosis, and Modulate Gene Expression in Rat Esophageal Epithelial Cells</title><author>Zikri, Nancy N ; Riedl, Kenneth M ; Wang, Li-Shu ; Lechner, John ; Schwartz, Steven J ; Stoner, Gary D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-ba470aab5e2a73da9c349d5eb5eb4279d33675196ee55ac151911b0f03e692393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>animal disease models</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Anthocyanins - analysis</topic><topic>Anthocyanins - chemistry</topic><topic>Anthocyanins - pharmacokinetics</topic><topic>Anthocyanins - pharmacology</topic><topic>anticarcinogenic activity</topic><topic>Antineoplastic Agents, Phytogenic - analysis</topic><topic>Antineoplastic Agents, Phytogenic - chemistry</topic><topic>Antineoplastic Agents, Phytogenic - pharmacokinetics</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>carcinogenesis</topic><topic>Caspases, Effector - genetics</topic><topic>Caspases, Effector - metabolism</topic><topic>cell culture</topic><topic>cell cycle</topic><topic>Cell Line, Tumor</topic><topic>cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Transformation, Neoplastic - chemically induced</topic><topic>chemical constituents of plants</topic><topic>cyanin</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>dietary exposure</topic><topic>Dose-Response Relationship, Drug</topic><topic>dried fruit</topic><topic>epidemiological studies</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>esophageal neoplasms</topic><topic>Esophageal Neoplasms - drug therapy</topic><topic>Esophageal Neoplasms - metabolism</topic><topic>esophagus</topic><topic>Feeding. Feeding behavior</topic><topic>freeze drying</topic><topic>Fruit - chemistry</topic><topic>fruit composition</topic><topic>fruit extracts</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Glucosides - analysis</topic><topic>Glucosides - chemistry</topic><topic>Glucosides - pharmacokinetics</topic><topic>Glucosides - pharmacology</topic><topic>Neoplasm Transplantation</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>nutrition-genotype interaction</topic><topic>nutritional intervention</topic><topic>Phytotherapy</topic><topic>Plant Extracts - administration & dosage</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Extracts - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Rosaceae - chemistry</topic><topic>Rubus occidentalis</topic><topic>small fruits</topic><topic>Time Factors</topic><topic>Tumor Burden</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zikri, Nancy N</creatorcontrib><creatorcontrib>Riedl, Kenneth M</creatorcontrib><creatorcontrib>Wang, Li-Shu</creatorcontrib><creatorcontrib>Lechner, John</creatorcontrib><creatorcontrib>Schwartz, Steven J</creatorcontrib><creatorcontrib>Stoner, Gary D</creatorcontrib><collection>AGRIS</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Nutrition and cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zikri, Nancy N</au><au>Riedl, Kenneth M</au><au>Wang, Li-Shu</au><au>Lechner, John</au><au>Schwartz, Steven J</au><au>Stoner, Gary D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Black Raspberry Components Inhibit Proliferation, Induce Apoptosis, and Modulate Gene Expression in Rat Esophageal Epithelial Cells</atitle><jtitle>Nutrition and cancer</jtitle><addtitle>Nutr Cancer</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>61</volume><issue>6</issue><spage>816</spage><epage>826</epage><pages>816-826</pages><issn>0163-5581</issn><eissn>1532-7914</eissn><coden>NUCADQ</coden><abstract>We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for their effects on growth, apoptosis, and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and proapoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells, whereas both anthocyanins downregulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract vs. when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo.</abstract><cop>Philadelphia, PA</cop><pub>Taylor & Francis Group</pub><pmid>20155622</pmid><doi>10.1080/01635580903285148</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nutrition and cancer, 2009-01, Vol.61 (6), p.816-826 |
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| subjects | animal disease models Animals Animals, Newborn Anthocyanins - analysis Anthocyanins - chemistry Anthocyanins - pharmacokinetics Anthocyanins - pharmacology anticarcinogenic activity Antineoplastic Agents, Phytogenic - analysis Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacokinetics Antineoplastic Agents, Phytogenic - pharmacology apoptosis Apoptosis - drug effects Biological and medical sciences carcinogenesis Caspases, Effector - genetics Caspases, Effector - metabolism cell culture cell cycle Cell Line, Tumor cell proliferation Cell Proliferation - drug effects Cell Transformation, Neoplastic - chemically induced chemical constituents of plants cyanin Cyclooxygenase 2 - genetics Cyclooxygenase 2 - metabolism dietary exposure Dose-Response Relationship, Drug dried fruit epidemiological studies Epithelial Cells - drug effects Epithelial Cells - metabolism esophageal neoplasms Esophageal Neoplasms - drug therapy Esophageal Neoplasms - metabolism esophagus Feeding. Feeding behavior freeze drying Fruit - chemistry fruit composition fruit extracts Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Neoplastic - drug effects Glucosides - analysis Glucosides - chemistry Glucosides - pharmacokinetics Glucosides - pharmacology Neoplasm Transplantation Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism nutrition-genotype interaction nutritional intervention Phytotherapy Plant Extracts - administration & dosage Plant Extracts - chemistry Plant Extracts - pharmacology Rats Rats, Inbred F344 Rosaceae - chemistry Rubus occidentalis small fruits Time Factors Tumor Burden Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Black Raspberry Components Inhibit Proliferation, Induce Apoptosis, and Modulate Gene Expression in Rat Esophageal Epithelial Cells |
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