Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis
Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we...
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2010-06, Vol.58 (11), p.7096-7103 |
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| creator | Wang, Hsiao−Chi Yang, Jen-Hung Hsieh, Shu-Chen Sheen, Lee-Yan |
| description | Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca2+ mobilization, and decreased mitochondrial membrane potential (ΔΨm). Western blot results showed the concordance for the expression of molecules involved in G2/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer. |
| doi_str_mv | 10.1021/jf100613x |
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However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca2+ mobilization, and decreased mitochondrial membrane potential (ΔΨm). Western blot results showed the concordance for the expression of molecules involved in G2/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/jf100613x</identifier><identifier>PMID: 20459099</identifier><identifier>CODEN: JAFCAU</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Allyl Compounds - pharmacology ; allyl sulfur compounds ; anticarcinogenic activity ; antioxidant activity ; apoptosis ; Apoptosis - drug effects ; biochemical pathways ; Biological and medical sciences ; carcinoma ; cell cycle ; Cell Cycle - drug effects ; Cell Division - drug effects ; Cell Line, Tumor ; cell proliferation ; Cell Proliferation - drug effects ; DNA damage ; DNA Damage - drug effects ; Down-Regulation - drug effects ; Food industries ; Fundamental and applied biological sciences. Psychology ; G2 Phase - drug effects ; garlic ; human cell lines ; human diseases ; human nutrition ; Humans ; keratinocytes ; melanoma ; membrane potential ; Molecular Nutrition ; oxidation ; p3 pathway ; Reactive Oxygen Species - metabolism ; skin ; Skin Neoplasms - drug therapy ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - physiopathology ; Sulfides - pharmacology ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; viability</subject><ispartof>Journal of agricultural and food chemistry, 2010-06, Vol.58 (11), p.7096-7103</ispartof><rights>Copyright © 2010 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jf100613x$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jf100613x$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22846743$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20459099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Hsiao−Chi</creatorcontrib><creatorcontrib>Yang, Jen-Hung</creatorcontrib><creatorcontrib>Hsieh, Shu-Chen</creatorcontrib><creatorcontrib>Sheen, Lee-Yan</creatorcontrib><title>Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca2+ mobilization, and decreased mitochondrial membrane potential (ΔΨm). Western blot results showed the concordance for the expression of molecules involved in G2/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer.</description><subject>Allyl Compounds - pharmacology</subject><subject>allyl sulfur compounds</subject><subject>anticarcinogenic activity</subject><subject>antioxidant activity</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>biochemical pathways</subject><subject>Biological and medical sciences</subject><subject>carcinoma</subject><subject>cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Tumor</subject><subject>cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>DNA damage</subject><subject>DNA Damage - drug effects</subject><subject>Down-Regulation - drug effects</subject><subject>Food industries</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>G2 Phase - drug effects</subject><subject>garlic</subject><subject>human cell lines</subject><subject>human diseases</subject><subject>human nutrition</subject><subject>Humans</subject><subject>keratinocytes</subject><subject>melanoma</subject><subject>membrane potential</subject><subject>Molecular Nutrition</subject><subject>oxidation</subject><subject>p3 pathway</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>skin</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - physiopathology</subject><subject>Sulfides - pharmacology</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>viability</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0U1vEzEQBmALgWgoHPgD4EvFaen4a9c-rlIIlVo4hJ6t6dqbOGzWwd4VLb8elwbqiw_zeOR5h5C3DD4y4Ox81zOAmom7Z2TBFIdKMaafkwWUYqVVzU7Iq5x3AKBVAy_JCQepDBizIL_bYbgf6Hoe-uB8ppfjNtyGiS79MNBVir-mLY09Xf8II13i2Pn0t5TptE1x3mzLAzd3U4jjA7v42tIL3OPG02vvAk7e0RU_v6ZtSj5PFEdH20M8TDGH_Jq86HHI_s3xPiU3nz99X36prr6tLpftVYWCwV0lmh6cNx3vPXOoOehymlrVjRGAXip0Go0yta57ybnjsjYeFBrPUQovxSn58Nj3kOLPuXzD7kPuyhA4-jhn2wjBeElPF_nuKOfbvXf2kMIe0739F1cBZ0eAucOhTyWRkJ8c17JupCju_aPrMVrcpGJu1hyYAKaV4pI_dcIu212c01gisAzsw0Lt_4WKP-Wpi3Y</recordid><startdate>20100609</startdate><enddate>20100609</enddate><creator>Wang, Hsiao−Chi</creator><creator>Yang, Jen-Hung</creator><creator>Hsieh, Shu-Chen</creator><creator>Sheen, Lee-Yan</creator><general>American Chemical Society</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>7X8</scope></search><sort><creationdate>20100609</creationdate><title>Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis</title><author>Wang, Hsiao−Chi ; Yang, Jen-Hung ; Hsieh, Shu-Chen ; Sheen, Lee-Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a310x-37f0de9c2fe1da820888876567930ae45ad8a959686f422d2469e05a9e2a43e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Allyl Compounds - pharmacology</topic><topic>allyl sulfur compounds</topic><topic>anticarcinogenic activity</topic><topic>antioxidant activity</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>biochemical pathways</topic><topic>Biological and medical sciences</topic><topic>carcinoma</topic><topic>cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Cell Line, Tumor</topic><topic>cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>DNA damage</topic><topic>DNA Damage - drug effects</topic><topic>Down-Regulation - drug effects</topic><topic>Food industries</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>G2 Phase - drug effects</topic><topic>garlic</topic><topic>human cell lines</topic><topic>human diseases</topic><topic>human nutrition</topic><topic>Humans</topic><topic>keratinocytes</topic><topic>melanoma</topic><topic>membrane potential</topic><topic>Molecular Nutrition</topic><topic>oxidation</topic><topic>p3 pathway</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>skin</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - physiopathology</topic><topic>Sulfides - pharmacology</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>viability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hsiao−Chi</creatorcontrib><creatorcontrib>Yang, Jen-Hung</creatorcontrib><creatorcontrib>Hsieh, Shu-Chen</creatorcontrib><creatorcontrib>Sheen, Lee-Yan</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>MEDLINE - Academic</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Hsiao−Chi</au><au>Yang, Jen-Hung</au><au>Hsieh, Shu-Chen</au><au>Sheen, Lee-Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2010-06-09</date><risdate>2010</risdate><volume>58</volume><issue>11</issue><spage>7096</spage><epage>7103</epage><pages>7096-7103</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><coden>JAFCAU</coden><abstract>Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca2+ mobilization, and decreased mitochondrial membrane potential (ΔΨm). Western blot results showed the concordance for the expression of molecules involved in G2/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>20459099</pmid><doi>10.1021/jf100613x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Allyl Compounds - pharmacology allyl sulfur compounds anticarcinogenic activity antioxidant activity apoptosis Apoptosis - drug effects biochemical pathways Biological and medical sciences carcinoma cell cycle Cell Cycle - drug effects Cell Division - drug effects Cell Line, Tumor cell proliferation Cell Proliferation - drug effects DNA damage DNA Damage - drug effects Down-Regulation - drug effects Food industries Fundamental and applied biological sciences. Psychology G2 Phase - drug effects garlic human cell lines human diseases human nutrition Humans keratinocytes melanoma membrane potential Molecular Nutrition oxidation p3 pathway Reactive Oxygen Species - metabolism skin Skin Neoplasms - drug therapy Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - physiopathology Sulfides - pharmacology Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism viability |
| title | Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis |
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