Proteomic Analysis of the Resistance to Aplidin in Human Cancer Cells

详细信息    查看全文

• 作者：Laura Gonzá ; lez-Santiago ; Patricia Alfonso ; Yajaira Suá ; rez ; Antonio Nú ; ñ ; ez ; Luis F. Garcí ; a-Ferná ; ndez ; Enrique Alvarez ; Alberto Muñ ; oz ; J. Ignacio Casal
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：6
• 期：4
• 页码：1286 - 1294
• 全文大小：700K
• 年卷期：v.6,no.4(April 2007)
• ISSN：1535-3907

文摘

Aplidin (plitidepsin) is an antitumoral agent that induces apoptosis via Rac1-JNK activation. A proteomicapproach using 2D-DIGE technology found 52 cytosolic and 39 membrane proteins differentiallyexpressed in wild-type and Aplidin-resistant HeLa cells, of which 39 and 27 were identified by MALDI-TOF mass spectrometry and database interrogation. A number of proteins involved in apoptosispathways were found to be deregulated. Alterations in Rab geranylgeranyltransferase, protein disulfideisomerase (PDI), cystathionine -lyase, ezrin, and cyclophilin A (CypA) were confirmed by immunoblotting. Moreover, the role of PDI and CypA in Aplidin resistance was functionally confirmed by usingthe inhibitor bacitracin and overexpression, respectively. These deregulated proteins are candidatesto mediate, at least partially, Aplidin action and might provide a route to the cells to escape the inductionof apoptosis by this drug.