Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes
Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various in vivo and in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and ap...
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| Veröffentlicht in: | Toxicology in vitro 2008-02, Vol.22 (1), p.87-95 |
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| creator | Lee, Jun Lee, Hwa-Jeong Park, Jong-Dae Lee, Sun-Kyung Lee, Sang-Im Lim, Hyun-Dae Lee, You-Mee Yun, Young-Gab Jeon, Byung-Hun Ree, In-Soo Jun, Chang-Duk Lee, Suk-Keun Kim, Eun-Cheol |
| description | Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various
in vivo and
in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining.
The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome
c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer. |
| doi_str_mv | 10.1016/j.tiv.2007.08.016 |
| format | Article |
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in vivo and
in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining.
The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome
c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2007.08.016</identifier><identifier>PMID: 17920232</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Blotting, Western ; Cell Cycle - drug effects ; Cell Division - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell-cycle arrest ; Chemoprevention ; Cyclins - drug effects ; Cyclins - metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation - drug effects ; Humans ; Immortalized keratinocytes ; Keratinocytes - drug effects ; Keratinocytes - pathology ; Mouth Neoplasms - drug therapy ; Neoplasm Staging ; Oral cancer ; Purified sulfur ; Sulfur Compounds - administration & dosage ; Sulfur Compounds - pharmacology ; Time Factors</subject><ispartof>Toxicology in vitro, 2008-02, Vol.22 (1), p.87-95</ispartof><rights>2007 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-12de2fec2cddcad99e92f09fa958d506bde89e87513700776515227bd0583c13</citedby><cites>FETCH-LOGICAL-c448t-12de2fec2cddcad99e92f09fa958d506bde89e87513700776515227bd0583c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0887233307002330$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17920232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jun</creatorcontrib><creatorcontrib>Lee, Hwa-Jeong</creatorcontrib><creatorcontrib>Park, Jong-Dae</creatorcontrib><creatorcontrib>Lee, Sun-Kyung</creatorcontrib><creatorcontrib>Lee, Sang-Im</creatorcontrib><creatorcontrib>Lim, Hyun-Dae</creatorcontrib><creatorcontrib>Lee, You-Mee</creatorcontrib><creatorcontrib>Yun, Young-Gab</creatorcontrib><creatorcontrib>Jeon, Byung-Hun</creatorcontrib><creatorcontrib>Ree, In-Soo</creatorcontrib><creatorcontrib>Jun, Chang-Duk</creatorcontrib><creatorcontrib>Lee, Suk-Keun</creatorcontrib><creatorcontrib>Kim, Eun-Cheol</creatorcontrib><title>Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes</title><title>Toxicology in vitro</title><addtitle>Toxicol In Vitro</addtitle><description>Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various
in vivo and
in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining.
The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome
c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer.</description><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Blotting, Western</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell-cycle arrest</subject><subject>Chemoprevention</subject><subject>Cyclins - drug effects</subject><subject>Cyclins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Immortalized keratinocytes</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - pathology</subject><subject>Mouth Neoplasms - drug therapy</subject><subject>Neoplasm Staging</subject><subject>Oral cancer</subject><subject>Purified sulfur</subject><subject>Sulfur Compounds - administration & dosage</subject><subject>Sulfur Compounds - pharmacology</subject><subject>Time Factors</subject><issn>0887-2333</issn><issn>1879-3177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9LAzEQxYMoWqsfwIvk5G3XSbbbZPEk4j8QvPQe0mTWpu5ma5IV6qc30oI3Pc3wePNgfo-QCwYlAza_XpfJfZYcQJQgy6wckAmToikqJsQhmYCUouBVVZ2Q0xjXAFBLDsfkhImGA6_4hOCtT64w2hsMVJuc59KWDi1dubdVt6WbMbjWoaVx7NoxUOep6_shJN25ryxrb2mf9zevfaKrsdeeDkF39B2DTs4PZpswnpGjVncRz_dzShYP94u7p-Ll9fH57valMLOZTAXjFnmLhhtrjbZNgw1voWl1U0tbw3xpUTYoRc0qkZ8W85rVnIulzX9VhlVTcrWL3YThY8SYVO-iwa7THocxKpERcSHgXyOHepYR1dnIdkYThhgDtmoTXK_DVjFQPx2otcrM1E8HCqTKSr653IePyx7t78Ueejbc7AyYUXw6DCoah7kB6wKapOzg_oj_Bj97mOM</recordid><startdate>20080201</startdate><enddate>20080201</enddate><creator>Lee, Jun</creator><creator>Lee, Hwa-Jeong</creator><creator>Park, Jong-Dae</creator><creator>Lee, Sun-Kyung</creator><creator>Lee, Sang-Im</creator><creator>Lim, Hyun-Dae</creator><creator>Lee, You-Mee</creator><creator>Yun, Young-Gab</creator><creator>Jeon, Byung-Hun</creator><creator>Ree, In-Soo</creator><creator>Jun, Chang-Duk</creator><creator>Lee, Suk-Keun</creator><creator>Kim, Eun-Cheol</creator><general>Elsevier Ltd</general><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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20080201</creationdate><title>Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes</title><author>Lee, Jun ; Lee, Hwa-Jeong ; Park, Jong-Dae ; Lee, Sun-Kyung ; Lee, Sang-Im ; Lim, Hyun-Dae ; Lee, You-Mee ; Yun, Young-Gab ; Jeon, Byung-Hun ; Ree, In-Soo ; Jun, Chang-Duk ; Lee, Suk-Keun ; Kim, Eun-Cheol</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-12de2fec2cddcad99e92f09fa958d506bde89e87513700776515227bd0583c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Blotting, Western</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell-cycle arrest</topic><topic>Chemoprevention</topic><topic>Cyclins - drug effects</topic><topic>Cyclins - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humans</topic><topic>Immortalized keratinocytes</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - pathology</topic><topic>Mouth Neoplasms - drug therapy</topic><topic>Neoplasm Staging</topic><topic>Oral cancer</topic><topic>Purified sulfur</topic><topic>Sulfur Compounds - administration & dosage</topic><topic>Sulfur Compounds - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Jun</creatorcontrib><creatorcontrib>Lee, Hwa-Jeong</creatorcontrib><creatorcontrib>Park, Jong-Dae</creatorcontrib><creatorcontrib>Lee, Sun-Kyung</creatorcontrib><creatorcontrib>Lee, Sang-Im</creatorcontrib><creatorcontrib>Lim, Hyun-Dae</creatorcontrib><creatorcontrib>Lee, You-Mee</creatorcontrib><creatorcontrib>Yun, Young-Gab</creatorcontrib><creatorcontrib>Jeon, Byung-Hun</creatorcontrib><creatorcontrib>Ree, In-Soo</creatorcontrib><creatorcontrib>Jun, Chang-Duk</creatorcontrib><creatorcontrib>Lee, Suk-Keun</creatorcontrib><creatorcontrib>Kim, Eun-Cheol</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicology in vitro</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Jun</au><au>Lee, Hwa-Jeong</au><au>Park, Jong-Dae</au><au>Lee, Sun-Kyung</au><au>Lee, Sang-Im</au><au>Lim, Hyun-Dae</au><au>Lee, You-Mee</au><au>Yun, Young-Gab</au><au>Jeon, Byung-Hun</au><au>Ree, In-Soo</au><au>Jun, Chang-Duk</au><au>Lee, Suk-Keun</au><au>Kim, Eun-Cheol</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes</atitle><jtitle>Toxicology in vitro</jtitle><addtitle>Toxicol In Vitro</addtitle><date>2008-02-01</date><risdate>2008</risdate><volume>22</volume><issue>1</issue><spage>87</spage><epage>95</epage><pages>87-95</pages><issn>0887-2333</issn><eissn>1879-3177</eissn><abstract>Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various
in vivo and
in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining.
The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome
c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>17920232</pmid><doi>10.1016/j.tiv.2007.08.016</doi><tpages>9</tpages></addata></record> |
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| subjects | Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Blotting, Western Cell Cycle - drug effects Cell Division - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cell-cycle arrest Chemoprevention Cyclins - drug effects Cyclins - metabolism Dose-Response Relationship, Drug Gene Expression Regulation - drug effects Humans Immortalized keratinocytes Keratinocytes - drug effects Keratinocytes - pathology Mouth Neoplasms - drug therapy Neoplasm Staging Oral cancer Purified sulfur Sulfur Compounds - administration & dosage Sulfur Compounds - pharmacology Time Factors |
| title | Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes |
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