Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion
Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is wor...
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| description | Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP. |
| doi_str_mv | 10.1371/journal.pone.0084610 |
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Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0084610</identifier><identifier>PMID: 24367681</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenosine Triphosphate - metabolism ; AMP ; AMP-Activated Protein Kinases ; Anticancer properties ; Antigens ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; ATP ; Beetles ; Bisbenzimidazole ; Blistering ; Blotting, Western ; Bone marrow ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; Cancer therapies ; Care and treatment ; Cell culture ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - drug effects ; Cytochrome ; Cytochrome c ; Cytochromes c - metabolism ; Deoxyribonucleic acid ; Depletion ; DNA ; DNA damage ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gallbladder ; Humans ; In Situ Nick-End Labeling ; Kinases ; Leukocytes ; Male ; Medical prognosis ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Micronucleus Tests ; Mitochondria ; Mitochondria - drug effects ; Norcantharidin ; Phosphatase ; Polyethylene glycol ; Proliferating cell nuclear antigen ; Proliferating Cell Nuclear Antigen - metabolism ; Prostate cancer ; Prostatic Neoplasms - drug therapy ; Protein kinase ; Proteins ; Reactive Oxygen Species - metabolism ; Superoxide Dismutase - metabolism</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e84610</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Shen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Shen et al 2013 Shen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-2b1f01b074dc37d477602fbd2288f94be6c32779f570d193d0f2a48859164c7d3</citedby><cites>FETCH-LOGICAL-c692t-2b1f01b074dc37d477602fbd2288f94be6c32779f570d193d0f2a48859164c7d3</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/PMC3868658/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868658/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24367681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Bo</creatorcontrib><creatorcontrib>He, Pei-Jie</creatorcontrib><creatorcontrib>Shao, Chun-Lin</creatorcontrib><title>Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>AMP</subject><subject>AMP-Activated Protein Kinases</subject><subject>Anticancer properties</subject><subject>Antigens</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>ATP</subject><subject>Beetles</subject><subject>Bisbenzimidazole</subject><subject>Blistering</subject><subject>Blotting, Western</subject><subject>Bone marrow</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cytochrome</subject><subject>Cytochrome c</subject><subject>Cytochromes c - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>Depletion</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Flow Cytometry</subject><subject>Gallbladder</subject><subject>Humans</subject><subject>In Situ Nick-End Labeling</subject><subject>Kinases</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Micronucleus Tests</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Norcantharidin</subject><subject>Phosphatase</subject><subject>Polyethylene glycol</subject><subject>Proliferating cell nuclear antigen</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Superoxide Dismutase - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1rFDEYhQdRbK3-A9EBQfBi13xNkrkRSv1aKC601tuQSTI7KbPJNMmI--_NutOyAwqSi4Q3z3uSnJyieAnBEmIG39_6MTjZLwfvzBIATigEj4pTWGO0oAjgx0frk-JZjLcAVJhT-rQ4QQRTRjk8Lfw3H5R0qZPBautK6_SojC4_3kBSlcr0fSkHPyQfbSxTF_y46cqr9fVia7SVKZNbm7zqvNPByr7Uu9iOTiXrXSmdLo0zYbMrtRl6sy8-L560so_mxTSfFTefP32_-Lq4XH9ZXZxfLhStUVqgBrYANoARrTDThDEKUNtohDhva9IYqjBirG4rBnR-pgYtkoTzqoaUKKbxWfH6oDv0PorJqyggoTUDsK5AJlYHQnt5K4ZgtzLshJdW_Cn4sBEyJKt6I4iSEGJINOKAkEbWXHLVYG0QawivSNb6MJ02NtkYZVwKsp-Jznec7cTG_xT5PziteBZ4MwkEfzeamP5x5YnayHwr61qfxdTWRiXOCeMIVgDgTC3_QuWhzdaqnJbW5vqs4d2sITPJ_EobOcYoVtdX_8-uf8zZt0dsZ2Sfuuj7cZ-DOAfJAVTBxxhM--AcBGIf9ns3xD7sYgp7bnt17PpD03268W-PGfnn</recordid><startdate>20131219</startdate><enddate>20131219</enddate><creator>Shen, Bo</creator><creator>He, Pei-Jie</creator><creator>Shao, Chun-Lin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131219</creationdate><title>Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion</title><author>Shen, Bo ; He, Pei-Jie ; Shao, Chun-Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-2b1f01b074dc37d477602fbd2288f94be6c32779f570d193d0f2a48859164c7d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>AMP</topic><topic>AMP-Activated Protein Kinases</topic><topic>Anticancer properties</topic><topic>Antigens</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>ATP</topic><topic>Beetles</topic><topic>Bisbenzimidazole</topic><topic>Blistering</topic><topic>Blotting, Western</topic><topic>Bone marrow</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cytochrome</topic><topic>Cytochrome c</topic><topic>Cytochromes c - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>Depletion</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Flow Cytometry</topic><topic>Gallbladder</topic><topic>Humans</topic><topic>In Situ Nick-End Labeling</topic><topic>Kinases</topic><topic>Leukocytes</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Micronucleus Tests</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Norcantharidin</topic><topic>Phosphatase</topic><topic>Polyethylene glycol</topic><topic>Proliferating cell nuclear antigen</topic><topic>Proliferating Cell Nuclear Antigen - metabolism</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Superoxide Dismutase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shen, Bo</creatorcontrib><creatorcontrib>He, Pei-Jie</creatorcontrib><creatorcontrib>Shao, Chun-Lin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24367681</pmid><doi>10.1371/journal.pone.0084610</doi><tpages>e84610</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine Triphosphate - metabolism AMP AMP-Activated Protein Kinases Anticancer properties Antigens Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects ATP Beetles Bisbenzimidazole Blistering Blotting, Western Bone marrow Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cancer therapies Care and treatment Cell culture Cell growth Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Cytochrome Cytochrome c Cytochromes c - metabolism Deoxyribonucleic acid Depletion DNA DNA damage Dose-Response Relationship, Drug Flow Cytometry Gallbladder Humans In Situ Nick-End Labeling Kinases Leukocytes Male Medical prognosis Membrane potential Membrane Potential, Mitochondrial - drug effects Micronucleus Tests Mitochondria Mitochondria - drug effects Norcantharidin Phosphatase Polyethylene glycol Proliferating cell nuclear antigen Proliferating Cell Nuclear Antigen - metabolism Prostate cancer Prostatic Neoplasms - drug therapy Protein kinase Proteins Reactive Oxygen Species - metabolism Superoxide Dismutase - metabolism |
| title | Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion |
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