Phenoxodiol Treatment Alters the Subsequent Response of ENOX2 (tNOX) and Growth of HeLa Cells to Paclitaxel and Cisplatin
Phenoxodiol is an experimental anticancer drug under development as a chemosensitizer intended to reverse multidrug resistance mechanisms in ovarian and prostate cancer cells to most standard cytotoxics. The putative molecular target of phenoxodiol is a cell-surface, tumor-specific NADH oxidase, ENO...
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| Veröffentlicht in: | Molecular biotechnology 2009-05, Vol.42 (1), p.100-109 |
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| creator | Morré, D. James McClain, Nicole Wu, L.-Y Kelly, Graham Morré, Dorothy M |
| description | Phenoxodiol is an experimental anticancer drug under development as a chemosensitizer intended to reverse multidrug resistance mechanisms in ovarian and prostate cancer cells to most standard cytotoxics. The putative molecular target of phenoxodiol is a cell-surface, tumor-specific NADH oxidase, ENOX2 (tNOX), with phenoxodiol having no apparent effect on the constitutive form of this enzyme ENOX1 (CNOX). Using ENOX2 as the target, this study was conducted to explore the temporal relationship between phenoxodiol and paclitaxel or cisplatin in achieving chemosensitization in HeLa cells which are relatively resistant to both paclitaxel and cisplatin. Sequential addition of phenoxodiol and paclitaxel or phenoxodiol and cisplatin showed greater inhibition of HeLa cell ENOX1 activity and growth compared to adding the drugs simultaneously or individually. In parallel, a similar chemosensitizing response of phenoxodiol for cisplatin was observed. ENOX1 was not affected and trans-platinum had no effect. With spent media from phenoxodiol-treated cells sensitivity was enhanced to both paclitaxel and cisplatin if the cells were first pretreated with phenoxodiol. Similar results were obtained with ENOX2-enriched preparations stripped from the surfaces of phenoxodiol-treated cells. In keeping with a speculative prion model, it seems as though the ENOX2 “remembers” the phenoxodiol and “teaches” other ENOX2 molecules to respond to paclitaxel and cisplatin as if phenoxodiol were still present. |
| doi_str_mv | 10.1007/s12033-008-9132-x |
| format | Article |
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James ; McClain, Nicole ; Wu, L.-Y ; Kelly, Graham ; Morré, Dorothy M</creator><creatorcontrib>Morré, D. James ; McClain, Nicole ; Wu, L.-Y ; Kelly, Graham ; Morré, Dorothy M</creatorcontrib><description>Phenoxodiol is an experimental anticancer drug under development as a chemosensitizer intended to reverse multidrug resistance mechanisms in ovarian and prostate cancer cells to most standard cytotoxics. The putative molecular target of phenoxodiol is a cell-surface, tumor-specific NADH oxidase, ENOX2 (tNOX), with phenoxodiol having no apparent effect on the constitutive form of this enzyme ENOX1 (CNOX). Using ENOX2 as the target, this study was conducted to explore the temporal relationship between phenoxodiol and paclitaxel or cisplatin in achieving chemosensitization in HeLa cells which are relatively resistant to both paclitaxel and cisplatin. Sequential addition of phenoxodiol and paclitaxel or phenoxodiol and cisplatin showed greater inhibition of HeLa cell ENOX1 activity and growth compared to adding the drugs simultaneously or individually. In parallel, a similar chemosensitizing response of phenoxodiol for cisplatin was observed. ENOX1 was not affected and trans-platinum had no effect. With spent media from phenoxodiol-treated cells sensitivity was enhanced to both paclitaxel and cisplatin if the cells were first pretreated with phenoxodiol. Similar results were obtained with ENOX2-enriched preparations stripped from the surfaces of phenoxodiol-treated cells. In keeping with a speculative prion model, it seems as though the ENOX2 “remembers” the phenoxodiol and “teaches” other ENOX2 molecules to respond to paclitaxel and cisplatin as if phenoxodiol were still present.</description><identifier>ISSN: 1073-6085</identifier><identifier>EISSN: 1559-0305</identifier><identifier>DOI: 10.1007/s12033-008-9132-x</identifier><identifier>PMID: 19156549</identifier><language>eng</language><publisher>New York: New York : Humana Press Inc</publisher><subject>Antineoplastic Agents - pharmacology ; Biochemistry ; Biological Techniques ; Biotechnology ; Cancer ; Cell Biology ; Cell Membrane - metabolism ; Cell Proliferation - drug effects ; Cells ; Chemistry ; Chemistry and Materials Science ; Cisplatin - pharmacology ; Culture Media, Conditioned - pharmacology ; Drug Resistance, Neoplasm - drug effects ; Drugs ; HeLa Cells ; Human Genetics ; Humans ; Hydrogen-Ion Concentration ; Isoflavones - pharmacology ; Microsomes - metabolism ; Molecular biology ; NADH, NADPH Oxidoreductases - drug effects ; NADH, NADPH Oxidoreductases - metabolism ; Paclitaxel - metabolism ; Paclitaxel - pharmacology ; Prostate cancer ; Protein Science ; Studies</subject><ispartof>Molecular biotechnology, 2009-05, Vol.42 (1), p.100-109</ispartof><rights>Humana Press 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-1eeb90d00d2e49a8aafc74379404d40cc47d4b9739118272123048f6481bf073</citedby><cites>FETCH-LOGICAL-c424t-1eeb90d00d2e49a8aafc74379404d40cc47d4b9739118272123048f6481bf073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12033-008-9132-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12033-008-9132-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19156549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morré, D. James</creatorcontrib><creatorcontrib>McClain, Nicole</creatorcontrib><creatorcontrib>Wu, L.-Y</creatorcontrib><creatorcontrib>Kelly, Graham</creatorcontrib><creatorcontrib>Morré, Dorothy M</creatorcontrib><title>Phenoxodiol Treatment Alters the Subsequent Response of ENOX2 (tNOX) and Growth of HeLa Cells to Paclitaxel and Cisplatin</title><title>Molecular biotechnology</title><addtitle>Mol Biotechnol</addtitle><addtitle>Mol Biotechnol</addtitle><description>Phenoxodiol is an experimental anticancer drug under development as a chemosensitizer intended to reverse multidrug resistance mechanisms in ovarian and prostate cancer cells to most standard cytotoxics. The putative molecular target of phenoxodiol is a cell-surface, tumor-specific NADH oxidase, ENOX2 (tNOX), with phenoxodiol having no apparent effect on the constitutive form of this enzyme ENOX1 (CNOX). Using ENOX2 as the target, this study was conducted to explore the temporal relationship between phenoxodiol and paclitaxel or cisplatin in achieving chemosensitization in HeLa cells which are relatively resistant to both paclitaxel and cisplatin. Sequential addition of phenoxodiol and paclitaxel or phenoxodiol and cisplatin showed greater inhibition of HeLa cell ENOX1 activity and growth compared to adding the drugs simultaneously or individually. In parallel, a similar chemosensitizing response of phenoxodiol for cisplatin was observed. ENOX1 was not affected and trans-platinum had no effect. With spent media from phenoxodiol-treated cells sensitivity was enhanced to both paclitaxel and cisplatin if the cells were first pretreated with phenoxodiol. Similar results were obtained with ENOX2-enriched preparations stripped from the surfaces of phenoxodiol-treated cells. In keeping with a speculative prion model, it seems as though the ENOX2 “remembers” the phenoxodiol and “teaches” other ENOX2 molecules to respond to paclitaxel and cisplatin as if phenoxodiol were still present.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Biochemistry</subject><subject>Biological Techniques</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Cisplatin - pharmacology</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drugs</subject><subject>HeLa Cells</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Isoflavones - pharmacology</subject><subject>Microsomes - metabolism</subject><subject>Molecular biology</subject><subject>NADH, NADPH Oxidoreductases - drug effects</subject><subject>NADH, NADPH Oxidoreductases - metabolism</subject><subject>Paclitaxel - metabolism</subject><subject>Paclitaxel - pharmacology</subject><subject>Prostate cancer</subject><subject>Protein Science</subject><subject>Studies</subject><issn>1073-6085</issn><issn>1559-0305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkU9v1DAQxSMEoqXwAbiAxQHBITBjO3F8rFb9g7SiFV0kbpaTTLqpsvHWdsT229dLVqrEAU5jeX7zZp5elr1F-IIA6mtADkLkAFWuUfB89yw7xqLQOQgonqc3KJGXUBVH2asQ7gA4FlK8zI5QY1EWUh9nD9drGt3Otb0b2MqTjRsaIzsdIvnA4prYzVQHup_2vz8obN0YiLmOnX2_-sXZp5jKZ2bHll149zuu961LWlq2oGFIAo5d22boo93R8Adb9GE72NiPr7MXnR0CvTnUk2x1frZaXObLq4tvi9Nl3kguY45EtYYWoOUkta2s7RolhdISZCuhaaRqZa2V0IgVVxy5AFl1payw7pL_k-zjLLv1LrkI0Wz60KTj7EhuCqZUyBG1-C-YlLkqRZHAD3-Bd27yY_JguChVuqOUCcIZarwLwVNntr7fWP9gEMw-PDOHZ1J4Zh-e2aWZdwfhqd5Q-zRxSCsBfAZCao235J82_0v1_TzUWWfsre-D-XnDAQVgyQGS9UfYcawK</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Morré, D. 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James</au><au>McClain, Nicole</au><au>Wu, L.-Y</au><au>Kelly, Graham</au><au>Morré, Dorothy M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenoxodiol Treatment Alters the Subsequent Response of ENOX2 (tNOX) and Growth of HeLa Cells to Paclitaxel and Cisplatin</atitle><jtitle>Molecular biotechnology</jtitle><stitle>Mol Biotechnol</stitle><addtitle>Mol Biotechnol</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>42</volume><issue>1</issue><spage>100</spage><epage>109</epage><pages>100-109</pages><issn>1073-6085</issn><eissn>1559-0305</eissn><abstract>Phenoxodiol is an experimental anticancer drug under development as a chemosensitizer intended to reverse multidrug resistance mechanisms in ovarian and prostate cancer cells to most standard cytotoxics. The putative molecular target of phenoxodiol is a cell-surface, tumor-specific NADH oxidase, ENOX2 (tNOX), with phenoxodiol having no apparent effect on the constitutive form of this enzyme ENOX1 (CNOX). Using ENOX2 as the target, this study was conducted to explore the temporal relationship between phenoxodiol and paclitaxel or cisplatin in achieving chemosensitization in HeLa cells which are relatively resistant to both paclitaxel and cisplatin. Sequential addition of phenoxodiol and paclitaxel or phenoxodiol and cisplatin showed greater inhibition of HeLa cell ENOX1 activity and growth compared to adding the drugs simultaneously or individually. In parallel, a similar chemosensitizing response of phenoxodiol for cisplatin was observed. ENOX1 was not affected and trans-platinum had no effect. With spent media from phenoxodiol-treated cells sensitivity was enhanced to both paclitaxel and cisplatin if the cells were first pretreated with phenoxodiol. Similar results were obtained with ENOX2-enriched preparations stripped from the surfaces of phenoxodiol-treated cells. In keeping with a speculative prion model, it seems as though the ENOX2 “remembers” the phenoxodiol and “teaches” other ENOX2 molecules to respond to paclitaxel and cisplatin as if phenoxodiol were still present.</abstract><cop>New York</cop><pub>New York : Humana Press Inc</pub><pmid>19156549</pmid><doi>10.1007/s12033-008-9132-x</doi><tpages>10</tpages></addata></record> |
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| subjects | Antineoplastic Agents - pharmacology Biochemistry Biological Techniques Biotechnology Cancer Cell Biology Cell Membrane - metabolism Cell Proliferation - drug effects Cells Chemistry Chemistry and Materials Science Cisplatin - pharmacology Culture Media, Conditioned - pharmacology Drug Resistance, Neoplasm - drug effects Drugs HeLa Cells Human Genetics Humans Hydrogen-Ion Concentration Isoflavones - pharmacology Microsomes - metabolism Molecular biology NADH, NADPH Oxidoreductases - drug effects NADH, NADPH Oxidoreductases - metabolism Paclitaxel - metabolism Paclitaxel - pharmacology Prostate cancer Protein Science Studies |
| title | Phenoxodiol Treatment Alters the Subsequent Response of ENOX2 (tNOX) and Growth of HeLa Cells to Paclitaxel and Cisplatin |
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