Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies
ABSTRACT In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightl...
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description | ABSTRACT
In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis‐related protein (MMP‐2, MMP‐9, and VEGF‐A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121–1132, 2016. |
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In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis‐related protein (MMP‐2, MMP‐9, and VEGF‐A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121–1132, 2016.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.22121</identifier><identifier>PMID: 25728215</identifier><identifier>CODEN: ETOXFH</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Apoptosis - drug effects ; arsenic trioxide ; Arsenicals ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cervical cancer ; Female ; Glutathione - metabolism ; HeLa Cells ; human cervical cancer cells ; Humans ; humic acid ; Humic Substances - toxicity ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mitosis - drug effects ; Oxides - toxicity ; Reactive Oxygen Species - metabolism ; Transplantation, Heterologous ; tumor progression ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - pathology ; Vascular Endothelial Growth Factor A</subject><ispartof>Environmental toxicology, 2016-09, Vol.31 (9), p.1121-1132</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4971-3f72099343b414fe58130d3c100dc840ef565cefa6b4ed3307ee61def5d13c9c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.22121$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.22121$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25728215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsai, Min-Ling</creatorcontrib><creatorcontrib>Yen, Cheng-Chieh</creatorcontrib><creatorcontrib>Lu, Fung-Jou</creatorcontrib><creatorcontrib>Ting, Hung-Chih</creatorcontrib><creatorcontrib>Chang, Horng-Rong</creatorcontrib><title>Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies</title><title>Environmental toxicology</title><addtitle>Environ. Toxicol</addtitle><description>ABSTRACT
In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis‐related protein (MMP‐2, MMP‐9, and VEGF‐A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121–1132, 2016.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>arsenic trioxide</subject><subject>Arsenicals</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cervical cancer</subject><subject>Female</subject><subject>Glutathione - metabolism</subject><subject>HeLa Cells</subject><subject>human cervical cancer cells</subject><subject>Humans</subject><subject>humic acid</subject><subject>Humic Substances - toxicity</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Mitosis - drug effects</subject><subject>Oxides - toxicity</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Transplantation, Heterologous</subject><subject>tumor progression</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Vascular Endothelial Growth Factor A</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1u1DAUhS1ERUthwQsgS2zYpPVP4iTsoC39UaFIDIKd5bFvwCWxW9sJM4_Dm9aZGbpg5Xuvv3N0dC9Cryg5ooSw4-RXR4xRRp-gA1oxVtSsbp5ualKUpKH76HmMt4SQVlTiGdpnVc0aRqsD9PfMTTZ4N4BLqu_XOEAPk3IJa-90HgaVrHfYd1iFCM5qnIL1K2sAK2fwr3HII6WtwXfBDz6BwWkcfJjbnwFi3KkzqBzWECarVY-1yu4h930f3-FLhyc7-Y2jnesUPI5pNBbiC7TXqT7Cy917iL59PFucXBTXN-eXJ--vC122NS14VzPStrzky5KWHVQN5cRwnRdkdFMS6CpRaeiUWJZgOCc1gKAmjw3lutX8EL3d-ubg9yPEJAcb53zKgR-jpA2tRFsKQjL65j_01o_B5XQzlVMI0daZer2jxuUARt4FO6iwlv-Wn4HjLfDH9rB-_KdEzleV-apyc1W5uPmxKbKi2CpsTLB6VKjwW4qa15X8_vlcfj39cnVxtfggP_EHJEimyA</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Tsai, Min-Ling</creator><creator>Yen, Cheng-Chieh</creator><creator>Lu, Fung-Jou</creator><creator>Ting, Hung-Chih</creator><creator>Chang, Horng-Rong</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope></search><sort><creationdate>201609</creationdate><title>Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies</title><author>Tsai, Min-Ling ; Yen, Cheng-Chieh ; Lu, Fung-Jou ; Ting, Hung-Chih ; Chang, Horng-Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4971-3f72099343b414fe58130d3c100dc840ef565cefa6b4ed3307ee61def5d13c9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>arsenic trioxide</topic><topic>Arsenicals</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cervical cancer</topic><topic>Female</topic><topic>Glutathione - metabolism</topic><topic>HeLa Cells</topic><topic>human cervical cancer cells</topic><topic>Humans</topic><topic>humic acid</topic><topic>Humic Substances - toxicity</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Mitosis - drug effects</topic><topic>Oxides - toxicity</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Transplantation, Heterologous</topic><topic>tumor progression</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Vascular Endothelial Growth Factor A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsai, Min-Ling</creatorcontrib><creatorcontrib>Yen, Cheng-Chieh</creatorcontrib><creatorcontrib>Lu, Fung-Jou</creatorcontrib><creatorcontrib>Ting, Hung-Chih</creatorcontrib><creatorcontrib>Chang, Horng-Rong</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsai, Min-Ling</au><au>Yen, Cheng-Chieh</au><au>Lu, Fung-Jou</au><au>Ting, Hung-Chih</au><au>Chang, Horng-Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ. Toxicol</addtitle><date>2016-09</date><risdate>2016</risdate><volume>31</volume><issue>9</issue><spage>1121</spage><epage>1132</epage><pages>1121-1132</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><coden>ETOXFH</coden><abstract>ABSTRACT
In a previous study, treatment at higher concentrations of arsenic trioxide or co‐exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis‐related protein (MMP‐2, MMP‐9, and VEGF‐A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co‐exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound‐healing activities, migration abilities, and MMP‐2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug‐treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP‐2, MMP‐9, and VEGF‐A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121–1132, 2016.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25728215</pmid><doi>10.1002/tox.22121</doi><tpages>12</tpages></addata></record> |
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subjects | Animals Apoptosis - drug effects arsenic trioxide Arsenicals Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Cell Survival - drug effects Cervical cancer Female Glutathione - metabolism HeLa Cells human cervical cancer cells Humans humic acid Humic Substances - toxicity Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Mice Mice, Inbred NOD Mice, SCID Mitosis - drug effects Oxides - toxicity Reactive Oxygen Species - metabolism Transplantation, Heterologous tumor progression Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - pathology Vascular Endothelial Growth Factor A |
title | Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies |
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