Role for PKC in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells
The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted react...
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Veröffentlicht in: | Journal of signal transduction 2010-06, Vol.2010, p.1-15 |
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creator | Ruvolo, Vivian R. Karanjeet, Kul B. Schuster, Todd F. Brown, Rhoderick Deng, Yibin Hinchcliffe, Edward Ruvolo, Peter P. |
description | The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted reactive oxygen species (ROS) generation. The antioxidant Vitamin C prevented fenretinide-induced PKC cleavage and protected cells from fenretinide. Suppression of PKC expression by shRNA sensitized cells to fenretinide-induced apoptosis possibly by a mechanism involving ROS production. A previous study demonstrated that fenretinide promotes degradation of antiapoptotic MCL-1 in ALL cells via JNK. Now we have found that fenretinide-induced MCL-1 degradation may involve PKC as cleavage of the kinase correlated with loss of MCL-1 even in cells when JNK was not activated. These results suggest that PKC may play a complex role in fenretinide-induced apoptosis and may be targeted in antileukemia strategies that utilize fenretinide. |
doi_str_mv | 10.1155/2010/584657 |
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In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted reactive oxygen species (ROS) generation. The antioxidant Vitamin C prevented fenretinide-induced PKC cleavage and protected cells from fenretinide. Suppression of PKC expression by shRNA sensitized cells to fenretinide-induced apoptosis possibly by a mechanism involving ROS production. A previous study demonstrated that fenretinide promotes degradation of antiapoptotic MCL-1 in ALL cells via JNK. Now we have found that fenretinide-induced MCL-1 degradation may involve PKC as cleavage of the kinase correlated with loss of MCL-1 even in cells when JNK was not activated. These results suggest that PKC may play a complex role in fenretinide-induced apoptosis and may be targeted in antileukemia strategies that utilize fenretinide.</description><identifier>ISSN: 2090-1739</identifier><identifier>EISSN: 2090-1747</identifier><identifier>DOI: 10.1155/2010/584657</identifier><language>eng</language><publisher>New York: Hindawi Limited</publisher><subject>Apoptosis ; Cancer ; Kinases ; Proteins</subject><ispartof>Journal of signal transduction, 2010-06, Vol.2010, p.1-15</ispartof><rights>Copyright © 2010 Vivian R. Ruvolo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1427-e388bef8b8faaa472f477237c3d46d5e05561a7b6aaf6cdd0d362c1d90ca39c53</citedby><cites>FETCH-LOGICAL-c1427-e388bef8b8faaa472f477237c3d46d5e05561a7b6aaf6cdd0d362c1d90ca39c53</cites><orcidid>0000-0002-7337-3604</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Ruvolo, Vivian R.</creatorcontrib><creatorcontrib>Karanjeet, Kul B.</creatorcontrib><creatorcontrib>Schuster, Todd F.</creatorcontrib><creatorcontrib>Brown, Rhoderick</creatorcontrib><creatorcontrib>Deng, Yibin</creatorcontrib><creatorcontrib>Hinchcliffe, Edward</creatorcontrib><creatorcontrib>Ruvolo, Peter P.</creatorcontrib><title>Role for PKC in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells</title><title>Journal of signal transduction</title><description>The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. 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These results suggest that PKC may play a complex role in fenretinide-induced apoptosis and may be targeted in antileukemia strategies that utilize fenretinide.</description><subject>Apoptosis</subject><subject>Cancer</subject><subject>Kinases</subject><subject>Proteins</subject><issn>2090-1739</issn><issn>2090-1747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNo9kE1LAzEURYMoWGpX_oHgVsbmO5llGawWRxTR9ZAmbzB1OhmT6aL_vi0V3-a-xeFeOAjdUvJAqZRzRiiZSyOU1BdowkhJCqqFvvz_eXmNZjlvyPFEybRRE7T6iB3gNib8_lLh0OMl9AnG0AcPxSv4YEfweDHEYYw55BNR77fDdwwe17D7gW2wuIKuyzfoqrVdhtlfTtHX8vGzei7qt6dVtagLRwXTBXBj1tCatWmttUKzVmjNuHbcC-UlECkVtXqtrG2V8554rpijviTO8tJJPkV3594hxd8d5LHZxF3qj5ONkYowWVJ-hO7PkEsx5wRtM6SwtWnfUNKcbDUnW83ZFj8AyElaxQ</recordid><startdate>20100608</startdate><enddate>20100608</enddate><creator>Ruvolo, Vivian R.</creator><creator>Karanjeet, Kul B.</creator><creator>Schuster, Todd F.</creator><creator>Brown, Rhoderick</creator><creator>Deng, Yibin</creator><creator>Hinchcliffe, Edward</creator><creator>Ruvolo, Peter P.</creator><general>Hindawi Limited</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8AL</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>JQ2</scope><scope>K7-</scope><scope>LK8</scope><scope>M0N</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-7337-3604</orcidid></search><sort><creationdate>20100608</creationdate><title>Role for PKC in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells</title><author>Ruvolo, Vivian R. ; 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In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted reactive oxygen species (ROS) generation. The antioxidant Vitamin C prevented fenretinide-induced PKC cleavage and protected cells from fenretinide. Suppression of PKC expression by shRNA sensitized cells to fenretinide-induced apoptosis possibly by a mechanism involving ROS production. A previous study demonstrated that fenretinide promotes degradation of antiapoptotic MCL-1 in ALL cells via JNK. Now we have found that fenretinide-induced MCL-1 degradation may involve PKC as cleavage of the kinase correlated with loss of MCL-1 even in cells when JNK was not activated. 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subjects | Apoptosis Cancer Kinases Proteins |
title | Role for PKC in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells |
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