LINCOVÁ, Eva, Aleš HAMPL, Zuzana PERNICOVÁ, Andrea STARŠÍCHOVÁ, Pavel KRČMÁŘ, Miroslav MACHALA, Alois KOZUBÍK a Karel SOUČEK. Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs. Biochemical Pharmacology. 2009, roč. 78, č. 6, s. 561-572. ISSN 0006-2952. |
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@article{869301, author = {Lincová, Eva and Hampl, Aleš and Pernicová, Zuzana and Staršíchová, Andrea and Krčmář, Pavel and Machala, Miroslav and Kozubík, Alois and Souček, Karel}, article_number = {6}, keywords = {NSAIDs; Protein kinase B/Akt; Akt2 isoform; PTEN; SHIP2; Anti proliferative effects}, language = {eng}, issn = {0006-2952}, journal = {Biochemical Pharmacology}, title = {Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs}, volume = {78}, year = {2009} }
TY - JOUR ID - 869301 AU - Lincová, Eva - Hampl, Aleš - Pernicová, Zuzana - Staršíchová, Andrea - Krčmář, Pavel - Machala, Miroslav - Kozubík, Alois - Souček, Karel PY - 2009 TI - Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs JF - Biochemical Pharmacology VL - 78 IS - 6 SP - 561-572 EP - 561-572 SN - 00062952 KW - NSAIDs KW - Protein kinase B/Akt KW - Akt2 isoform KW - PTEN KW - SHIP2 KW - Anti proliferative effects N2 - The basis of antitumor effects of non-steroidal anti-inflammatory drugs (NSAIDs) is not understood yet. Here we observed significant differences in sensitivity of cancer epithelial cell lines to COX-independent anti proliferative effects of NSAIDs. The prostate cancer cell line LNCaP, lacking both critical enzymes in the negative control of PKB/Akt activation, PTEN and SHIP2, was the most sensitive to these effects. We found that p53 protein and its signalling pathway is not involved in early antiproliferative action of the selected NSAID-indomethacin. RNAi provided evidence for the involvement of p21(Cip1/Waf1). We also found that indomethacin activated PKB/Akt and induced nuclear localisation of p21(Cip1/Waf1) and Akt2 isoform. Our data suggest novel mechanisms of NSAIDs anti proliferative action in cancer epithelial cells, which depends on the status of negative regulation of the PKB/Akt pathway and the isoform-specific action of Akt2. ER -
LINCOVÁ, Eva, Aleš HAMPL, Zuzana PERNICOVÁ, Andrea STARŠÍCHOVÁ, Pavel KRČMÁŘ, Miroslav MACHALA, Alois KOZUBÍK a Karel SOUČEK. Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs. \textit{Biochemical Pharmacology}. 2009, roč.~78, č.~6, s.~561-572. ISSN~0006-2952.
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