An Adaptation System to Avoid Apoptosis via Autophagy Under Hypoxic Conditions in Pancreatic Cancer Cells
Pancreatic cancer tissue is a hypoxic environment resistant to anticancer drugs. This study examined the role of autophagy as a response to hypoxic stress in pancreatic cancer. Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimic...
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| Veröffentlicht in: | Anticancer research 2017-09, Vol.37 (9), p.4927-4934 |
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| container_issue | 9 |
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| container_title | Anticancer research |
| container_volume | 37 |
| creator | Owada, Satoshi Ito, Kanako Endo, Hitoshi Shida, Yukari Okada, Chisa Nezu, Takahiro Tatemichi, Masayuki |
| description | Pancreatic cancer tissue is a hypoxic environment resistant to anticancer drugs. This study examined the role of autophagy as a response to hypoxic stress in pancreatic cancer.
Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimicking agent. Protein expression and cytotoxicity assays were performed to determine the effect of hypoxia on autophagy.
When pancreatic cancer cells were exposed to hypoxia, autophagy was induced. The autophagy-inducing signal was dependent on the AMPK pathway. Inhibition of autophagy in a hypoxic state induced a remarkable cytotoxicity and enhanced apoptosis. When an AMPK inhibitor was added, cytotoxicity was observed in the hypoxic environment.
The induced autophagy, dependent on the AMPK pathway, is a necessary survival strategy adopted by pancreatic cancer cells to adapt to hypoxic stress, and could be an attractive target for drug development. |
| doi_str_mv | 10.21873/anticanres.11902 |
| format | Article |
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Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimicking agent. Protein expression and cytotoxicity assays were performed to determine the effect of hypoxia on autophagy.
When pancreatic cancer cells were exposed to hypoxia, autophagy was induced. The autophagy-inducing signal was dependent on the AMPK pathway. Inhibition of autophagy in a hypoxic state induced a remarkable cytotoxicity and enhanced apoptosis. When an AMPK inhibitor was added, cytotoxicity was observed in the hypoxic environment.
The induced autophagy, dependent on the AMPK pathway, is a necessary survival strategy adopted by pancreatic cancer cells to adapt to hypoxic stress, and could be an attractive target for drug development.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>DOI: 10.21873/anticanres.11902</identifier><identifier>PMID: 28870914</identifier><language>eng</language><publisher>Greece</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Autophagy ; Cell Hypoxia ; Cell Proliferation - drug effects ; Humans ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Signal Transduction - drug effects ; Tumor Cells, Cultured</subject><ispartof>Anticancer research, 2017-09, Vol.37 (9), p.4927-4934</ispartof><rights>Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-fe5fd8904ce8727b20336d8bd1322ae9508fd53aed41aeafcc8a17d67cf8b6d93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28870914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Owada, Satoshi</creatorcontrib><creatorcontrib>Ito, Kanako</creatorcontrib><creatorcontrib>Endo, Hitoshi</creatorcontrib><creatorcontrib>Shida, Yukari</creatorcontrib><creatorcontrib>Okada, Chisa</creatorcontrib><creatorcontrib>Nezu, Takahiro</creatorcontrib><creatorcontrib>Tatemichi, Masayuki</creatorcontrib><title>An Adaptation System to Avoid Apoptosis via Autophagy Under Hypoxic Conditions in Pancreatic Cancer Cells</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Pancreatic cancer tissue is a hypoxic environment resistant to anticancer drugs. This study examined the role of autophagy as a response to hypoxic stress in pancreatic cancer.
Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimicking agent. Protein expression and cytotoxicity assays were performed to determine the effect of hypoxia on autophagy.
When pancreatic cancer cells were exposed to hypoxia, autophagy was induced. The autophagy-inducing signal was dependent on the AMPK pathway. Inhibition of autophagy in a hypoxic state induced a remarkable cytotoxicity and enhanced apoptosis. When an AMPK inhibitor was added, cytotoxicity was observed in the hypoxic environment.
The induced autophagy, dependent on the AMPK pathway, is a necessary survival strategy adopted by pancreatic cancer cells to adapt to hypoxic stress, and could be an attractive target for drug development.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy</subject><subject>Cell Hypoxia</subject><subject>Cell Proliferation - drug effects</subject><subject>Humans</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Signal Transduction - drug effects</subject><subject>Tumor Cells, Cultured</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAUhoMobk5_gDeSS28689E26WUp6gRBQXdd0iTVyJrUJB3231u3qVfnwHnel8MDwCVGS4I5ozfCRiOF9TosMS4QOQJzzAqcsIyiYzBHJEMJQyibgbMQPhDK84LTUzAjnDNU4HQOTGlhqUQfRTTOwpcxRN3B6GC5dUbBsnd9dMEEuDUClkN0_bt4G-HaKu3hauzdl5GwclaZn3yAxsJnYaXXU990mNaJq_RmE87BSSs2QV8c5gKs725fq1Xy-HT_UJWPiaRpGpNWZ63iBUql5oywhiBKc8UbhSkhQhcZ4q3KqNAqxUKLVkouMFM5ky1vclXQBbje9_befQ46xLozQU4fCKvdEGpc0IzjlOd0QvEeld6F4HVb9950wo81RvXOcP1vuN4ZnjJXh_qh6bT6S_wqpd-lZnt8</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Owada, Satoshi</creator><creator>Ito, Kanako</creator><creator>Endo, Hitoshi</creator><creator>Shida, Yukari</creator><creator>Okada, Chisa</creator><creator>Nezu, Takahiro</creator><creator>Tatemichi, Masayuki</creator><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>7X8</scope></search><sort><creationdate>20170901</creationdate><title>An Adaptation System to Avoid Apoptosis via Autophagy Under Hypoxic Conditions in Pancreatic Cancer Cells</title><author>Owada, Satoshi ; Ito, Kanako ; Endo, Hitoshi ; Shida, Yukari ; Okada, Chisa ; Nezu, Takahiro ; Tatemichi, Masayuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-fe5fd8904ce8727b20336d8bd1322ae9508fd53aed41aeafcc8a17d67cf8b6d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Autophagy</topic><topic>Cell Hypoxia</topic><topic>Cell Proliferation - drug effects</topic><topic>Humans</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Signal Transduction - drug effects</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Owada, Satoshi</creatorcontrib><creatorcontrib>Ito, Kanako</creatorcontrib><creatorcontrib>Endo, Hitoshi</creatorcontrib><creatorcontrib>Shida, Yukari</creatorcontrib><creatorcontrib>Okada, Chisa</creatorcontrib><creatorcontrib>Nezu, Takahiro</creatorcontrib><creatorcontrib>Tatemichi, Masayuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Owada, Satoshi</au><au>Ito, Kanako</au><au>Endo, Hitoshi</au><au>Shida, Yukari</au><au>Okada, Chisa</au><au>Nezu, Takahiro</au><au>Tatemichi, Masayuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Adaptation System to Avoid Apoptosis via Autophagy Under Hypoxic Conditions in Pancreatic Cancer Cells</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>37</volume><issue>9</issue><spage>4927</spage><epage>4934</epage><pages>4927-4934</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Pancreatic cancer tissue is a hypoxic environment resistant to anticancer drugs. This study examined the role of autophagy as a response to hypoxic stress in pancreatic cancer.
Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimicking agent. Protein expression and cytotoxicity assays were performed to determine the effect of hypoxia on autophagy.
When pancreatic cancer cells were exposed to hypoxia, autophagy was induced. The autophagy-inducing signal was dependent on the AMPK pathway. Inhibition of autophagy in a hypoxic state induced a remarkable cytotoxicity and enhanced apoptosis. When an AMPK inhibitor was added, cytotoxicity was observed in the hypoxic environment.
The induced autophagy, dependent on the AMPK pathway, is a necessary survival strategy adopted by pancreatic cancer cells to adapt to hypoxic stress, and could be an attractive target for drug development.</abstract><cop>Greece</cop><pmid>28870914</pmid><doi>10.21873/anticanres.11902</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antineoplastic Agents - pharmacology Apoptosis - drug effects Autophagy Cell Hypoxia Cell Proliferation - drug effects Humans Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Signal Transduction - drug effects Tumor Cells, Cultured |
| title | An Adaptation System to Avoid Apoptosis via Autophagy Under Hypoxic Conditions in Pancreatic Cancer Cells |
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