Evaluation of Cytotoxic and Apoptotic Effects of Individual and Mixed 7‑Ketophytosterol Oxides on Human Intestinal Carcinoma Cells
Phytosterol oxidation products (POPs) are constituents of the human diet. Definitive information on the toxic or biological effects of POPs is limited and in some cases contradictory. This study evaluates the cytotoxicity of four individual 7-ketophytosterol oxides, including 7-ketositosterol (7K-SI...
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Veröffentlicht in: | Journal of agricultural and food chemistry 2015-01, Vol.63 (3), p.1035-1041 |
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creator | Gao, Junlan Chen, Shaopeng Zhang, Lele Cheng, Beijiu Xu, An Wu, Lijun Zhang, Xin |
description | Phytosterol oxidation products (POPs) are constituents of the human diet. Definitive information on the toxic or biological effects of POPs is limited and in some cases contradictory. This study evaluates the cytotoxicity of four individual 7-ketophytosterol oxides, including 7-ketositosterol (7K-SI), 7-ketocampesterol (7K-CA), 7-ketobrassicasterol (7K-BR), 7-ketostigmasterol (7K-ST), and a mixture of 7-ketophytosterols (7K-MIX) toward a human intestinal carcinoma (HIC) cell line. Results showed that all tested compounds reduced cell proliferation in a dose-dependent manner; especially 7K-SI and 7K-CA exhibited higher activities. Both compounds increased early apoptotic cells and caused cell cycle arrest in the G1 phase with cell accumulation in the S phase. No evidence of cell death was observed induced by 7K-ST and 7K-MIX. Furthermore, 7K-SI, 7K-CA, and 7K-BR induced apoptosis by enhancing caspase-3 activity and the modulatory effects of Bcl-2, while 7K-ST and 7K-MIX did not involve caspase-3 activation and Bcl-2 down-regulation. |
doi_str_mv | 10.1021/jf505079v |
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Definitive information on the toxic or biological effects of POPs is limited and in some cases contradictory. This study evaluates the cytotoxicity of four individual 7-ketophytosterol oxides, including 7-ketositosterol (7K-SI), 7-ketocampesterol (7K-CA), 7-ketobrassicasterol (7K-BR), 7-ketostigmasterol (7K-ST), and a mixture of 7-ketophytosterols (7K-MIX) toward a human intestinal carcinoma (HIC) cell line. Results showed that all tested compounds reduced cell proliferation in a dose-dependent manner; especially 7K-SI and 7K-CA exhibited higher activities. Both compounds increased early apoptotic cells and caused cell cycle arrest in the G1 phase with cell accumulation in the S phase. No evidence of cell death was observed induced by 7K-ST and 7K-MIX. Furthermore, 7K-SI, 7K-CA, and 7K-BR induced apoptosis by enhancing caspase-3 activity and the modulatory effects of Bcl-2, while 7K-ST and 7K-MIX did not involve caspase-3 activation and Bcl-2 down-regulation.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/jf505079v</identifier><identifier>PMID: 25542134</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Antineoplastic Agents - pharmacology ; apoptosis ; Apoptosis - drug effects ; carcinoma ; Caspase 3 - metabolism ; caspase-3 ; cell cycle checkpoints ; Cell Cycle Checkpoints - drug effects ; Cell Line, Tumor ; cell proliferation ; Cell Proliferation - drug effects ; cytotoxicity ; diet ; dose response ; G1 Phase - drug effects ; Humans ; interphase ; Intestinal Neoplasms - chemistry ; Intestinal Neoplasms - pathology ; neoplasm cells ; oxidation ; oxides ; phytosterols ; Proto-Oncogene Proteins c-bcl-2 - analysis ; S Phase - drug effects ; Sitosterols - pharmacology</subject><ispartof>Journal of agricultural and food chemistry, 2015-01, Vol.63 (3), p.1035-1041</ispartof><rights>Copyright © American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a339t-17c6df9bba631e17ebeee817c92a7179d100d43f9800f0ad93da63da4e8b3853</citedby><cites>FETCH-LOGICAL-a339t-17c6df9bba631e17ebeee817c92a7179d100d43f9800f0ad93da63da4e8b3853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jf505079v$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jf505079v$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27074,27922,27923,56736,56786</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25542134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Junlan</creatorcontrib><creatorcontrib>Chen, Shaopeng</creatorcontrib><creatorcontrib>Zhang, Lele</creatorcontrib><creatorcontrib>Cheng, Beijiu</creatorcontrib><creatorcontrib>Xu, An</creatorcontrib><creatorcontrib>Wu, Lijun</creatorcontrib><creatorcontrib>Zhang, Xin</creatorcontrib><title>Evaluation of Cytotoxic and Apoptotic Effects of Individual and Mixed 7‑Ketophytosterol Oxides on Human Intestinal Carcinoma Cells</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Phytosterol oxidation products (POPs) are constituents of the human diet. Definitive information on the toxic or biological effects of POPs is limited and in some cases contradictory. This study evaluates the cytotoxicity of four individual 7-ketophytosterol oxides, including 7-ketositosterol (7K-SI), 7-ketocampesterol (7K-CA), 7-ketobrassicasterol (7K-BR), 7-ketostigmasterol (7K-ST), and a mixture of 7-ketophytosterols (7K-MIX) toward a human intestinal carcinoma (HIC) cell line. Results showed that all tested compounds reduced cell proliferation in a dose-dependent manner; especially 7K-SI and 7K-CA exhibited higher activities. Both compounds increased early apoptotic cells and caused cell cycle arrest in the G1 phase with cell accumulation in the S phase. No evidence of cell death was observed induced by 7K-ST and 7K-MIX. Furthermore, 7K-SI, 7K-CA, and 7K-BR induced apoptosis by enhancing caspase-3 activity and the modulatory effects of Bcl-2, while 7K-ST and 7K-MIX did not involve caspase-3 activation and Bcl-2 down-regulation.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>carcinoma</subject><subject>Caspase 3 - metabolism</subject><subject>caspase-3</subject><subject>cell cycle checkpoints</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Line, Tumor</subject><subject>cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>cytotoxicity</subject><subject>diet</subject><subject>dose response</subject><subject>G1 Phase - drug effects</subject><subject>Humans</subject><subject>interphase</subject><subject>Intestinal Neoplasms - chemistry</subject><subject>Intestinal Neoplasms - pathology</subject><subject>neoplasm cells</subject><subject>oxidation</subject><subject>oxides</subject><subject>phytosterols</subject><subject>Proto-Oncogene Proteins c-bcl-2 - analysis</subject><subject>S Phase - drug effects</subject><subject>Sitosterols - pharmacology</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0LFOwzAQBmALgWgpDLwAZGFgCJyTuklGFBVaUdSBMkeX2AZXaRzFTtVuDLwAr8iT4BLoxGSd_d2d_BNyTuGGQkBvl5IBgyhZH5A-ZQH4jNL4kPTBPfoxG9EeOTFmCQAxi-CY9ALGhgENh33yMV5j2aJVuvK09NKt1VZvVOFhxb27WteudtVYSlFYsyPTiqu14i2WP-ZJbQT3oq_3z0dhdf3mBhgrGl16843iwrVU3qRdYeUarTBWVa4xxaZQlV6hl4qyNKfkSGJpxNnvOSCL-_Einfiz-cM0vZv5GIaJ9WlUjLhM8hxHIRU0ErkQIna3SYARjRJOAfgwlEkMIAF5EnInOQ5FnIcxCwfkuhtbNNqYRsisbtQKm21GIdsFme2DdPais3WbrwTfy7_kHLjsgESd4WujTPbyHAAdAdAAEgicuOoEFiZb6rZxPzf_rPoGhDuGZw</recordid><startdate>20150128</startdate><enddate>20150128</enddate><creator>Gao, Junlan</creator><creator>Chen, Shaopeng</creator><creator>Zhang, Lele</creator><creator>Cheng, Beijiu</creator><creator>Xu, An</creator><creator>Wu, Lijun</creator><creator>Zhang, Xin</creator><general>American Chemical Society</general><general>American Chemical Society, Books and Journals Division</general><scope>FBQ</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></search><sort><creationdate>20150128</creationdate><title>Evaluation of Cytotoxic and Apoptotic Effects of Individual and Mixed 7‑Ketophytosterol Oxides on Human Intestinal Carcinoma Cells</title><author>Gao, Junlan ; Chen, Shaopeng ; Zhang, Lele ; Cheng, Beijiu ; Xu, An ; Wu, Lijun ; Zhang, Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a339t-17c6df9bba631e17ebeee817c92a7179d100d43f9800f0ad93da63da4e8b3853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>carcinoma</topic><topic>Caspase 3 - metabolism</topic><topic>caspase-3</topic><topic>cell cycle checkpoints</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Line, Tumor</topic><topic>cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>cytotoxicity</topic><topic>diet</topic><topic>dose response</topic><topic>G1 Phase - drug effects</topic><topic>Humans</topic><topic>interphase</topic><topic>Intestinal Neoplasms - chemistry</topic><topic>Intestinal Neoplasms - pathology</topic><topic>neoplasm cells</topic><topic>oxidation</topic><topic>oxides</topic><topic>phytosterols</topic><topic>Proto-Oncogene Proteins c-bcl-2 - analysis</topic><topic>S Phase - drug effects</topic><topic>Sitosterols - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gao, Junlan</creatorcontrib><creatorcontrib>Chen, Shaopeng</creatorcontrib><creatorcontrib>Zhang, Lele</creatorcontrib><creatorcontrib>Cheng, Beijiu</creatorcontrib><creatorcontrib>Xu, An</creatorcontrib><creatorcontrib>Wu, Lijun</creatorcontrib><creatorcontrib>Zhang, Xin</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gao, Junlan</au><au>Chen, Shaopeng</au><au>Zhang, Lele</au><au>Cheng, Beijiu</au><au>Xu, An</au><au>Wu, Lijun</au><au>Zhang, Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Cytotoxic and Apoptotic Effects of Individual and Mixed 7‑Ketophytosterol Oxides on Human Intestinal Carcinoma Cells</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2015-01-28</date><risdate>2015</risdate><volume>63</volume><issue>3</issue><spage>1035</spage><epage>1041</epage><pages>1035-1041</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>Phytosterol oxidation products (POPs) are constituents of the human diet. Definitive information on the toxic or biological effects of POPs is limited and in some cases contradictory. This study evaluates the cytotoxicity of four individual 7-ketophytosterol oxides, including 7-ketositosterol (7K-SI), 7-ketocampesterol (7K-CA), 7-ketobrassicasterol (7K-BR), 7-ketostigmasterol (7K-ST), and a mixture of 7-ketophytosterols (7K-MIX) toward a human intestinal carcinoma (HIC) cell line. Results showed that all tested compounds reduced cell proliferation in a dose-dependent manner; especially 7K-SI and 7K-CA exhibited higher activities. Both compounds increased early apoptotic cells and caused cell cycle arrest in the G1 phase with cell accumulation in the S phase. No evidence of cell death was observed induced by 7K-ST and 7K-MIX. Furthermore, 7K-SI, 7K-CA, and 7K-BR induced apoptosis by enhancing caspase-3 activity and the modulatory effects of Bcl-2, while 7K-ST and 7K-MIX did not involve caspase-3 activation and Bcl-2 down-regulation.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>25542134</pmid><doi>10.1021/jf505079v</doi><tpages>7</tpages></addata></record> |
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subjects | Antineoplastic Agents - pharmacology apoptosis Apoptosis - drug effects carcinoma Caspase 3 - metabolism caspase-3 cell cycle checkpoints Cell Cycle Checkpoints - drug effects Cell Line, Tumor cell proliferation Cell Proliferation - drug effects cytotoxicity diet dose response G1 Phase - drug effects Humans interphase Intestinal Neoplasms - chemistry Intestinal Neoplasms - pathology neoplasm cells oxidation oxides phytosterols Proto-Oncogene Proteins c-bcl-2 - analysis S Phase - drug effects Sitosterols - pharmacology |
title | Evaluation of Cytotoxic and Apoptotic Effects of Individual and Mixed 7‑Ketophytosterol Oxides on Human Intestinal Carcinoma Cells |
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