Multiple defects in negative regulation of the PKB/Akt pathway
sensitise human cancer cells to the antiproliferative effect of
non-steroidal anti-inflammatory drugs

J 2009

Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs

LINCOVÁ, Eva; Aleš HAMPL; Zuzana PERNICOVÁ; Andrea STARŠÍCHOVÁ; Pavel KRČMÁŘ et al.

Základní údaje

Originální název

Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs

Autoři

LINCOVÁ, Eva; Aleš HAMPL; Zuzana PERNICOVÁ; Andrea STARŠÍCHOVÁ; Pavel KRČMÁŘ; Miroslav MACHALA; Alois KOZUBÍK a Karel SOUČEK

Vydání

Biochemical Pharmacology, 2009, 0006-2952

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.254

Označené pro přenos do RIV

Organizační jednotka

Lékařská fakulta

UT WoS

000268877400003

Klíčová slova anglicky

NSAIDs; Protein kinase B/Akt; Akt2 isoform; PTEN; SHIP2; Anti proliferative effects

Změněno: 8. 3. 2010 10:45, Ing. Lucia Ráheľová

Anotace

V originále

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.

Citovat

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.

@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.

Přehled o publikaci