XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells
Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this...
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| Veröffentlicht in: | Environmental toxicology 2017-11, Vol.32 (11), p.2371-2378 |
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| creator | Lee, You‐Jin Park, Bong‐Soo Park, Hae‐Ryoun Yu, Su‐Bin Kang, Hae‐Mi Kim, In‐Ryoung |
| description | Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent. |
| doi_str_mv | 10.1002/tox.22450 |
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Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.22450</identifier><identifier>PMID: 28722333</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>active ingredients ; Anticancer properties ; antineoplastic activity ; Antineoplastic Agents, Phytogenic - pharmacology ; Antitumor activity ; Apoptosis ; Apoptosis - drug effects ; Autophagy ; Autophagy - drug effects ; Benzoquinones - pharmacology ; Biochemical markers ; biomarkers ; Cancer ; Carcinoma, Squamous Cell - drug therapy ; Caspase ; caspases ; Cell death ; Cell Line, Tumor ; Cells ; Chemical compounds ; embelin ; Herbal medicine ; Humans ; Inhibitors ; Mortality ; mouth neoplasms ; neoplasm cells ; Neoplasms ; Oral cancer ; Oral squamous cell carcinoma ; Phagocytosis ; Phagosomes - ultrastructure ; Pharmacology ; Squamous cell carcinoma ; therapeutics ; Tongue ; Tongue Neoplasms - drug therapy ; Vacuoles ; X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors ; XIAP inhibitor ; XIAP protein</subject><ispartof>Environmental toxicology, 2017-11, Vol.32 (11), p.2371-2378</ispartof><rights>2017 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc.</rights><rights>2017 Wiley Periodicals, Inc.</rights><rights>2017 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5130-e403d5468d4ddbe44fdaa2015b5a69159db75ece7d01f597f1b904846459b9d3</citedby><cites>FETCH-LOGICAL-c5130-e403d5468d4ddbe44fdaa2015b5a69159db75ece7d01f597f1b904846459b9d3</cites><orcidid>0000-0003-0232-0385</orcidid></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.22450$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.22450$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28722333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, You‐Jin</creatorcontrib><creatorcontrib>Park, Bong‐Soo</creatorcontrib><creatorcontrib>Park, Hae‐Ryoun</creatorcontrib><creatorcontrib>Yu, Su‐Bin</creatorcontrib><creatorcontrib>Kang, Hae‐Mi</creatorcontrib><creatorcontrib>Kim, In‐Ryoung</creatorcontrib><title>XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.</description><subject>active ingredients</subject><subject>Anticancer properties</subject><subject>antineoplastic activity</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Benzoquinones - pharmacology</subject><subject>Biochemical markers</subject><subject>biomarkers</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Caspase</subject><subject>caspases</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Chemical compounds</subject><subject>embelin</subject><subject>Herbal medicine</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Mortality</subject><subject>mouth neoplasms</subject><subject>neoplasm cells</subject><subject>Neoplasms</subject><subject>Oral cancer</subject><subject>Oral squamous cell carcinoma</subject><subject>Phagocytosis</subject><subject>Phagosomes - ultrastructure</subject><subject>Pharmacology</subject><subject>Squamous cell carcinoma</subject><subject>therapeutics</subject><subject>Tongue</subject><subject>Tongue Neoplasms - drug therapy</subject><subject>Vacuoles</subject><subject>X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors</subject><subject>XIAP inhibitor</subject><subject>XIAP protein</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1u1TAQhS0EoqWw4AWQJTawSDt2bCfeIFUVP5UqlcVddGc5ttO4SuzUToC-Pe5NqQAJsZoZ-9PRnDkIvSZwTADoyRJ_HFPKODxBh4RTWjW0aZ_ue6gYtOQAvcj5BgCk4OI5OqBtQ2ld14coXJ2ffsU-DL7zS0zYTZ0bfSgvdjUuY70ucR70tTdYB4v1HOclLmUybhyxdXoZCouHddIBx6RHnG9XPcU1b4TRyfgQJ70f80v0rNdjdq8e6hHaffq4O_tSXVx-Pj87vagMJzVUjkFtOROtZdZ2jrHeak2B8I5rIQmXtmu4M66xQHoum550EljLBOOyk7Y-Qh822XntJmeNC0tZTc3JTzrdqai9-vMn-EFdx29KsIa2LSkC7x4EUrxdXV7U5PO9Ax1c8aZouSXnHMT_USIp1JJywQr69i_0Jq4plEMUihOgooa2UO83yqSYc3L9494E1H3equSt9nkX9s3vRh_JXwEX4GQDvvvR3f1bSe0urzbJn5iptbY</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Lee, You‐Jin</creator><creator>Park, Bong‐Soo</creator><creator>Park, Hae‐Ryoun</creator><creator>Yu, Su‐Bin</creator><creator>Kang, Hae‐Mi</creator><creator>Kim, In‐Ryoung</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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><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><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0232-0385</orcidid></search><sort><creationdate>201711</creationdate><title>XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells</title><author>Lee, You‐Jin ; Park, Bong‐Soo ; Park, Hae‐Ryoun ; Yu, Su‐Bin ; Kang, Hae‐Mi ; Kim, In‐Ryoung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5130-e403d5468d4ddbe44fdaa2015b5a69159db75ece7d01f597f1b904846459b9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>active ingredients</topic><topic>Anticancer properties</topic><topic>antineoplastic activity</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>Benzoquinones - pharmacology</topic><topic>Biochemical markers</topic><topic>biomarkers</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Caspase</topic><topic>caspases</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cells</topic><topic>Chemical compounds</topic><topic>embelin</topic><topic>Herbal medicine</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Mortality</topic><topic>mouth neoplasms</topic><topic>neoplasm cells</topic><topic>Neoplasms</topic><topic>Oral cancer</topic><topic>Oral squamous cell carcinoma</topic><topic>Phagocytosis</topic><topic>Phagosomes - ultrastructure</topic><topic>Pharmacology</topic><topic>Squamous cell carcinoma</topic><topic>therapeutics</topic><topic>Tongue</topic><topic>Tongue Neoplasms - drug therapy</topic><topic>Vacuoles</topic><topic>X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors</topic><topic>XIAP inhibitor</topic><topic>XIAP protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, You‐Jin</creatorcontrib><creatorcontrib>Park, Bong‐Soo</creatorcontrib><creatorcontrib>Park, Hae‐Ryoun</creatorcontrib><creatorcontrib>Yu, Su‐Bin</creatorcontrib><creatorcontrib>Kang, Hae‐Mi</creatorcontrib><creatorcontrib>Kim, In‐Ryoung</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, You‐Jin</au><au>Park, Bong‐Soo</au><au>Park, Hae‐Ryoun</au><au>Yu, Su‐Bin</au><au>Kang, Hae‐Mi</au><au>Kim, In‐Ryoung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2017-11</date><risdate>2017</risdate><volume>32</volume><issue>11</issue><spage>2371</spage><epage>2378</epage><pages>2371-2378</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28722333</pmid><doi>10.1002/tox.22450</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0232-0385</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | active ingredients Anticancer properties antineoplastic activity Antineoplastic Agents, Phytogenic - pharmacology Antitumor activity Apoptosis Apoptosis - drug effects Autophagy Autophagy - drug effects Benzoquinones - pharmacology Biochemical markers biomarkers Cancer Carcinoma, Squamous Cell - drug therapy Caspase caspases Cell death Cell Line, Tumor Cells Chemical compounds embelin Herbal medicine Humans Inhibitors Mortality mouth neoplasms neoplasm cells Neoplasms Oral cancer Oral squamous cell carcinoma Phagocytosis Phagosomes - ultrastructure Pharmacology Squamous cell carcinoma therapeutics Tongue Tongue Neoplasms - drug therapy Vacuoles X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors XIAP inhibitor XIAP protein |
| title | XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells |
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