J 2010

The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12

ROUBALOVÁ, Eva; Veronika KVARDOVÁ; Roman HRSTKA; Šárka BOŘILOVÁ; Eva MICHALOVÁ et al.

Základní údaje

Originální název

The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12

Autoři

ROUBALOVÁ, Eva; Veronika KVARDOVÁ; Roman HRSTKA; Šárka BOŘILOVÁ; Eva MICHALOVÁ; Lenka ZDRAŽILOVÁ DUBSKÁ; Petra SCHARTLMUELLER; Petr SOVA a Bořivoj VOJTĚŠEK

Vydání

Investigational New Drugs, DORDRECHT, SPRINGER, 2010, 0167-6997

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.007

Označené pro přenos do RIV

Ne
Změněno: 15. 10. 2014 14:29, MUDr. RNDr. Michal Řiháček, Ph.D., EuSpLM

Anotace

V originále

In this study, we characterized the effects of LA-12 on tumor cell lines possessing wild type p53 and on p53-deficient/mutant cell lines and the results were compared to those obtained using cisplatin. We have determined changes of p53 levels, of its transcriptional activity, of its posttranscriptional modifications and the effect of the treatment on the cell cycle, on the induction of apoptosis and on gene expression. LA-12 induces weak accumulation of both transcriptionally active p53 tumor suppressor and of p21(WAF1/CIP1) protein. LA-12 and cisplatin also significantly differ in their effects on apoptosis and cell cycle and on gene expression spectra in studied cell lines. LA-12 induces higher apoptosis levels in comparison with those induced by cisplatin, especially in p53-deficient H1299 cells and in MCF-7DD cells with transcriptionally inactive p53. We suggest that LA-12-mediated apoptosis is not fully dependent on p53. This confirms the therapeutic potential of LA-12 as a more potent cytostatic agent for both tumor cells expressing wild type p53 and for p53-deficient or mutant cells.