title: Interaction of cisplatin, paclitaxel and adriamycin with the tumor suppressor PTEN.
abstract: Due to its pivotal role in signal transduction, the universal tumor suppressor PTEN (also termed MMAC or TEP) is one of the putative candidates for involvement in tumorigenesis of several tissues. Although involvement of PTEN in tumorigenesis was shown in different tissues, no data are available concerning PTEN activity in response to antineoplastic agents. Therefore, we assayed the PTEN activity exposed to either blank medium or the commonly used anti-cancer drugs cisplatin, adriamycin or paclitaxel, respectively, in three different concentrations. PTEN activity was determined using the Malachite Green assay basing upon dephosphorylation of phosphatidylinositol-3,4,5-triphosphate (PIP3) by the PTEN enzyme and subsequent determination of inorganic phosphate released. Although the three different anti-cancer drugs assayed act with different cellular modes, the antineoplastics influenced PTEN activity in a similar manner: at low concentrations tested all three antineoplastics significantly increased PTEN activity. However, increasing drug concentrations exhibited a decline but not a total loss of PTEN activity. The data indicate that PTEN activity is increased following cytotoxic drug exposure and, thereby, exhibits its suppressive function. However, the decrease of PTEN activity in response to increasing drug concentrations suggests an aberration of total functional activity. As far as the regulative checkpoint PTEN is abolished, tumor cells might evade cell death pathways resulting in increased proliferation of cancer cells. This might be a general event in refractory tumor cells surviving chemotherapy.
authors.affiliation: Department of Gynecology and Obstetics, University of Cologne, 50924 Cologne, Germany. thomas.schoendorf@medizin.uni-koeln.de
authors.forename: T
authors.initials: T
authors.lastname: Schöndorf
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: U J
authors.initials: UJ
authors.lastname: Göhring
authors.forename: B
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: H
authors.initials: H
authors.lastname: Kolhagen
authors.forename: C M
authors.initials: CM
authors.lastname: Kurbacher
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology; D051059:PTEN Phosphohydrolase; D017239:Paclitaxel / Q000494:pharmacology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018129:Phosphatidylinositol Phosphates; D025521:Tumor Suppressor Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D004317:Doxorubicin; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017239:Paclitaxel; D002945:Cisplatin