Dichloroacetate and metformin synergistically suppress the growth of ovarian cancer cells
Both dichloroacetate (DCA) and metformin (Met) have shown promising antitumor efficacy by regulating cancer cell metabolism. However, the DCA-mediated protective autophagy and Met-induced lactate accumulation limit their tumor-killing potential respectively. So overcoming the corresponding shortages...
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| Veröffentlicht in: | Oncotarget 2016-09, Vol.7 (37), p.59458-59470 |
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| creator | Li, Bo Li, Xinzhe Ni, Zhenhong Zhang, Yan Zeng, Yijun Yan, Xiaohuan Huang, Yan He, Jintao Lyu, Xilin Wu, Yaran Wang, Yuting Zheng, Yingru He, Fengtian |
| description | Both dichloroacetate (DCA) and metformin (Met) have shown promising antitumor efficacy by regulating cancer cell metabolism. However, the DCA-mediated protective autophagy and Met-induced lactate accumulation limit their tumor-killing potential respectively. So overcoming the corresponding shortages will improve their therapeutic effects. In the present study, we found that DCA and Met synergistically inhibited the growth and enhanced the apoptosis of ovarian cancer cells. Interestingly, we for the first time revealed that Met sensitized DCA via dramatically attenuating DCA-induced Mcl-1 protein and protective autophagy, while DCA sensitized Met through markedly alleviating Met-induced excessive lactate accumulation and glucose consumption. The in vivo experiments in nude mice also showed that DCA and Met synergistically suppressed the growth of xenograft ovarian tumors. These results may pave a way for developing novel strategies for the treatment of ovarian cancer based on the combined use of DCA and Met. |
| doi_str_mv | 10.18632/oncotarget.10694 |
| format | Article |
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However, the DCA-mediated protective autophagy and Met-induced lactate accumulation limit their tumor-killing potential respectively. So overcoming the corresponding shortages will improve their therapeutic effects. In the present study, we found that DCA and Met synergistically inhibited the growth and enhanced the apoptosis of ovarian cancer cells. Interestingly, we for the first time revealed that Met sensitized DCA via dramatically attenuating DCA-induced Mcl-1 protein and protective autophagy, while DCA sensitized Met through markedly alleviating Met-induced excessive lactate accumulation and glucose consumption. The in vivo experiments in nude mice also showed that DCA and Met synergistically suppressed the growth of xenograft ovarian tumors. These results may pave a way for developing novel strategies for the treatment of ovarian cancer based on the combined use of DCA and Met.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.10694</identifier><identifier>PMID: 27449090</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Autophagy ; Cell Line, Tumor ; Dichloroacetic Acid - therapeutic use ; Drug Synergism ; Drug Therapy, Combination ; Female ; Growth Inhibitors - therapeutic use ; Humans ; Lactic Acid - metabolism ; Metformin - therapeutic use ; Mice ; Mice, Nude ; Ovarian Neoplasms - drug therapy ; Research Paper ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2016-09, Vol.7 (37), p.59458-59470</ispartof><rights>Copyright: © 2016 Li et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-2d1f94af2ce4143cadae92bd8c4f6fac8185284a068592cf2fd27195768354543</citedby><cites>FETCH-LOGICAL-c356t-2d1f94af2ce4143cadae92bd8c4f6fac8185284a068592cf2fd27195768354543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312324/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312324/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27449090$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Bo</creatorcontrib><creatorcontrib>Li, Xinzhe</creatorcontrib><creatorcontrib>Ni, Zhenhong</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Zeng, Yijun</creatorcontrib><creatorcontrib>Yan, Xiaohuan</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>He, Jintao</creatorcontrib><creatorcontrib>Lyu, Xilin</creatorcontrib><creatorcontrib>Wu, Yaran</creatorcontrib><creatorcontrib>Wang, Yuting</creatorcontrib><creatorcontrib>Zheng, Yingru</creatorcontrib><creatorcontrib>He, Fengtian</creatorcontrib><title>Dichloroacetate and metformin synergistically suppress the growth of ovarian cancer cells</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Both dichloroacetate (DCA) and metformin (Met) have shown promising antitumor efficacy by regulating cancer cell metabolism. However, the DCA-mediated protective autophagy and Met-induced lactate accumulation limit their tumor-killing potential respectively. So overcoming the corresponding shortages will improve their therapeutic effects. In the present study, we found that DCA and Met synergistically inhibited the growth and enhanced the apoptosis of ovarian cancer cells. Interestingly, we for the first time revealed that Met sensitized DCA via dramatically attenuating DCA-induced Mcl-1 protein and protective autophagy, while DCA sensitized Met through markedly alleviating Met-induced excessive lactate accumulation and glucose consumption. The in vivo experiments in nude mice also showed that DCA and Met synergistically suppressed the growth of xenograft ovarian tumors. These results may pave a way for developing novel strategies for the treatment of ovarian cancer based on the combined use of DCA and Met.</description><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Cell Line, Tumor</subject><subject>Dichloroacetic Acid - therapeutic use</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Growth Inhibitors - therapeutic use</subject><subject>Humans</subject><subject>Lactic Acid - metabolism</subject><subject>Metformin - therapeutic use</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Research Paper</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkbtOLDEMhiMEAgQ8AA1KSbMwuc0kzZEQdwmJBgqqyGSc3RzNJEuSBe3bs9zBjS35929bHyH7rDliuhX8OEWXKuQp1iPWtEaukW1mpJlwpcT6r3qL7JXyv1mFkp3mZpNs8U5K05hmmzycBTcbUk7gsEJFCrGnI1af8hgiLcuIeRpKDQ6GYUnLYj7PWAqtM6TTnF7qjCZP0zPkAJE6iA4zdTgMZZdseBgK7n3mHXJ_cX53ejW5ub28Pj25mTih2jrhPfNGgucOJZPCQQ9o-GOvnfStB6eZVlxLaFqtDHee-553zKiu1UJJJcUO-ffhO188jtg7jDXDYOc5jJCXNkGwfzsxzOw0PVslGBf8zeDw0yCnpwWWasdQ3l6AiGlRLNO87YTUHV9J2YfU5VRKRv-9hjX2nYr9oWLfqaxmDn7f9z3xxUC8AhhajjE</recordid><startdate>20160913</startdate><enddate>20160913</enddate><creator>Li, Bo</creator><creator>Li, Xinzhe</creator><creator>Ni, Zhenhong</creator><creator>Zhang, Yan</creator><creator>Zeng, Yijun</creator><creator>Yan, Xiaohuan</creator><creator>Huang, Yan</creator><creator>He, Jintao</creator><creator>Lyu, Xilin</creator><creator>Wu, Yaran</creator><creator>Wang, Yuting</creator><creator>Zheng, Yingru</creator><creator>He, Fengtian</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160913</creationdate><title>Dichloroacetate and metformin synergistically suppress the growth of ovarian cancer cells</title><author>Li, Bo ; Li, Xinzhe ; Ni, Zhenhong ; Zhang, Yan ; Zeng, Yijun ; Yan, Xiaohuan ; Huang, Yan ; He, Jintao ; Lyu, Xilin ; Wu, Yaran ; Wang, Yuting ; Zheng, Yingru ; He, Fengtian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-2d1f94af2ce4143cadae92bd8c4f6fac8185284a068592cf2fd27195768354543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Cell Line, Tumor</topic><topic>Dichloroacetic Acid - therapeutic use</topic><topic>Drug Synergism</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Growth Inhibitors - therapeutic use</topic><topic>Humans</topic><topic>Lactic Acid - metabolism</topic><topic>Metformin - therapeutic use</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Research Paper</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Li, Bo</creatorcontrib><creatorcontrib>Li, Xinzhe</creatorcontrib><creatorcontrib>Ni, Zhenhong</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Zeng, Yijun</creatorcontrib><creatorcontrib>Yan, Xiaohuan</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>He, Jintao</creatorcontrib><creatorcontrib>Lyu, Xilin</creatorcontrib><creatorcontrib>Wu, Yaran</creatorcontrib><creatorcontrib>Wang, Yuting</creatorcontrib><creatorcontrib>Zheng, Yingru</creatorcontrib><creatorcontrib>He, Fengtian</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Bo</au><au>Li, Xinzhe</au><au>Ni, Zhenhong</au><au>Zhang, Yan</au><au>Zeng, Yijun</au><au>Yan, Xiaohuan</au><au>Huang, Yan</au><au>He, Jintao</au><au>Lyu, Xilin</au><au>Wu, Yaran</au><au>Wang, Yuting</au><au>Zheng, Yingru</au><au>He, Fengtian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dichloroacetate and metformin synergistically suppress the growth of ovarian cancer cells</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-09-13</date><risdate>2016</risdate><volume>7</volume><issue>37</issue><spage>59458</spage><epage>59470</epage><pages>59458-59470</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Both dichloroacetate (DCA) and metformin (Met) have shown promising antitumor efficacy by regulating cancer cell metabolism. However, the DCA-mediated protective autophagy and Met-induced lactate accumulation limit their tumor-killing potential respectively. So overcoming the corresponding shortages will improve their therapeutic effects. In the present study, we found that DCA and Met synergistically inhibited the growth and enhanced the apoptosis of ovarian cancer cells. Interestingly, we for the first time revealed that Met sensitized DCA via dramatically attenuating DCA-induced Mcl-1 protein and protective autophagy, while DCA sensitized Met through markedly alleviating Met-induced excessive lactate accumulation and glucose consumption. The in vivo experiments in nude mice also showed that DCA and Met synergistically suppressed the growth of xenograft ovarian tumors. These results may pave a way for developing novel strategies for the treatment of ovarian cancer based on the combined use of DCA and Met.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27449090</pmid><doi>10.18632/oncotarget.10694</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - therapeutic use Apoptosis Autophagy Cell Line, Tumor Dichloroacetic Acid - therapeutic use Drug Synergism Drug Therapy, Combination Female Growth Inhibitors - therapeutic use Humans Lactic Acid - metabolism Metformin - therapeutic use Mice Mice, Nude Ovarian Neoplasms - drug therapy Research Paper Xenograft Model Antitumor Assays |
| title | Dichloroacetate and metformin synergistically suppress the growth of ovarian cancer cells |
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