Induction of autophagy by sphingosine kinase 1 inhibitor PF-543 in head and neck squamous cell carcinoma cells
Sphingosine kinase 1 (SphK1) overexpressed in head and neck squamous cell carcinoma (SCC) regulates tumor growth. The effects of PF-543, a specific SphK1 inhibitor, on human SCC cells were examined. The proportion of viable cells after PF-543 treatment decreased in a time- and dose-dependent manner,...
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| Veröffentlicht in: | Cell death discovery 2017-08, Vol.3 (1), p.17047-17047, Article 17047 |
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| creator | Hamada, Masakazu Kameyama, Hiroyasu Iwai, Soichi Yura, Yoshiaki |
| description | Sphingosine kinase 1 (SphK1) overexpressed in head and neck squamous cell carcinoma (SCC) regulates tumor growth. The effects of PF-543, a specific SphK1 inhibitor, on human SCC cells were examined. The proportion of viable cells after PF-543 treatment decreased in a time- and dose-dependent manner, and cell death occurred in SphK1-expressing SCC cells. Flow cytometry analysis revealed that PF-543 induced both necrosis and apoptosis. PF-543 also induced granular accumulation of LC3 and conversion from LC3-I to LC3-II, which was blocked by autophagy inhibitors, wortmannin, 3-methyladenine (3-MA), and bafilomycin A1. Treatment of head and neck SCC cells with autophagy inhibitors and PF-543 increased the proportion of cells with necrosis and apoptosis, indicating that autophagy acts to promote cell survival. Reactive oxygen species (ROS) scavenger reduced the cytotoxicity of PF-543. These results demonstrated that PF-543 induces apoptosis, necrosis, and autophagy in human head and neck SCC cells, and that autophagy antagonizes either necrosis or apoptosis. |
| doi_str_mv | 10.1038/cddiscovery.2017.47 |
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The effects of PF-543, a specific SphK1 inhibitor, on human SCC cells were examined. The proportion of viable cells after PF-543 treatment decreased in a time- and dose-dependent manner, and cell death occurred in SphK1-expressing SCC cells. Flow cytometry analysis revealed that PF-543 induced both necrosis and apoptosis. PF-543 also induced granular accumulation of LC3 and conversion from LC3-I to LC3-II, which was blocked by autophagy inhibitors, wortmannin, 3-methyladenine (3-MA), and bafilomycin A1. Treatment of head and neck SCC cells with autophagy inhibitors and PF-543 increased the proportion of cells with necrosis and apoptosis, indicating that autophagy acts to promote cell survival. Reactive oxygen species (ROS) scavenger reduced the cytotoxicity of PF-543. 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The effects of PF-543, a specific SphK1 inhibitor, on human SCC cells were examined. The proportion of viable cells after PF-543 treatment decreased in a time- and dose-dependent manner, and cell death occurred in SphK1-expressing SCC cells. Flow cytometry analysis revealed that PF-543 induced both necrosis and apoptosis. PF-543 also induced granular accumulation of LC3 and conversion from LC3-I to LC3-II, which was blocked by autophagy inhibitors, wortmannin, 3-methyladenine (3-MA), and bafilomycin A1. Treatment of head and neck SCC cells with autophagy inhibitors and PF-543 increased the proportion of cells with necrosis and apoptosis, indicating that autophagy acts to promote cell survival. Reactive oxygen species (ROS) scavenger reduced the cytotoxicity of PF-543. 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Kameyama, Hiroyasu ; Iwai, Soichi ; Yura, Yoshiaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-c15d12e30fbf30136b71cc510282a22253a76dc9be46094b4b06f81a0c88bce33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/67/1665</topic><topic>631/80/82/39/2345</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Cycle Analysis</topic><topic>Cell death</topic><topic>Cell survival</topic><topic>Cytotoxicity</topic><topic>Enzyme inhibitors</topic><topic>Flow cytometry</topic><topic>Gangrene</topic><topic>Head & neck cancer</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Necrosis</topic><topic>Phagocytosis</topic><topic>Reactive oxygen species</topic><topic>Sphingosine kinase</topic><topic>Squamous cell carcinoma</topic><topic>Stem Cells</topic><topic>Wortmannin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamada, Masakazu</creatorcontrib><creatorcontrib>Kameyama, Hiroyasu</creatorcontrib><creatorcontrib>Iwai, Soichi</creatorcontrib><creatorcontrib>Yura, Yoshiaki</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death discovery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamada, Masakazu</au><au>Kameyama, Hiroyasu</au><au>Iwai, Soichi</au><au>Yura, Yoshiaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of autophagy by sphingosine kinase 1 inhibitor PF-543 in head and neck squamous cell carcinoma cells</atitle><jtitle>Cell death discovery</jtitle><stitle>Cell Death Discov</stitle><addtitle>Cell Death Discov</addtitle><date>2017-08-14</date><risdate>2017</risdate><volume>3</volume><issue>1</issue><spage>17047</spage><epage>17047</epage><pages>17047-17047</pages><artnum>17047</artnum><issn>2058-7716</issn><eissn>2058-7716</eissn><abstract>Sphingosine kinase 1 (SphK1) overexpressed in head and neck squamous cell carcinoma (SCC) regulates tumor growth. The effects of PF-543, a specific SphK1 inhibitor, on human SCC cells were examined. The proportion of viable cells after PF-543 treatment decreased in a time- and dose-dependent manner, and cell death occurred in SphK1-expressing SCC cells. Flow cytometry analysis revealed that PF-543 induced both necrosis and apoptosis. PF-543 also induced granular accumulation of LC3 and conversion from LC3-I to LC3-II, which was blocked by autophagy inhibitors, wortmannin, 3-methyladenine (3-MA), and bafilomycin A1. Treatment of head and neck SCC cells with autophagy inhibitors and PF-543 increased the proportion of cells with necrosis and apoptosis, indicating that autophagy acts to promote cell survival. Reactive oxygen species (ROS) scavenger reduced the cytotoxicity of PF-543. These results demonstrated that PF-543 induces apoptosis, necrosis, and autophagy in human head and neck SCC cells, and that autophagy antagonizes either necrosis or apoptosis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29109864</pmid><doi>10.1038/cddiscovery.2017.47</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/1665 631/80/82/39/2345 Apoptosis Autophagy Biochemistry Biomedical and Life Sciences Cell Biology Cell Cycle Analysis Cell death Cell survival Cytotoxicity Enzyme inhibitors Flow cytometry Gangrene Head & neck cancer Kinases Life Sciences Necrosis Phagocytosis Reactive oxygen species Sphingosine kinase Squamous cell carcinoma Stem Cells Wortmannin |
| title | Induction of autophagy by sphingosine kinase 1 inhibitor PF-543 in head and neck squamous cell carcinoma cells |
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