| HRSTKA, Roman, Darren J POWELL, Veronika KVARDOVA, Eva ROUBALOVÁ, Karima BOUROUGAA, Marco M CANDEIAS, Petr SOVA, Frantisek ZAK, Robin FAHRAEUS a Bořivoj VOJTĚŠEK. The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatin. ANTI-CANCER DRUGS. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS, 2008, roč. 19, č. 4, s. 369-379. ISSN 0959-4973. |
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@article{1088266,
author = {Hrstka, Roman and Powell, Darren J and Kvardova, Veronika and Roubalová, Eva and Bourougaa, Karima and Candeias, Marco M and Sova, Petr and Zak, Frantisek and Fahraeus, Robin and Vojtěšek, Bořivoj},
article_location = {PHILADELPHIA},
article_number = {4},
keywords = {cisplatin; LA-12; p53; p53/47},
language = {eng},
issn = {0959-4973},
journal = {ANTI-CANCER DRUGS},
title = {The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatin},
volume = {19},
year = {2008}
}
TY - JOUR
ID - 1088266
AU - Hrstka, Roman - Powell, Darren J - Kvardova, Veronika - Roubalová, Eva - Bourougaa, Karima - Candeias, Marco M - Sova, Petr - Zak, Frantisek - Fahraeus, Robin - Vojtěšek, Bořivoj
PY - 2008
TI - The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatin
JF - ANTI-CANCER DRUGS
VL - 19
IS - 4
SP - 369-379
EP - 369-379
PB - LIPPINCOTT WILLIAMS & WILKINS
SN - 09594973
KW - cisplatin
KW - LA-12
KW - p53
KW - p53/47
N2 - The platinum(II)-based complex cisplatin is one of the most frequently used antiturnour agents; however, a high incidence of harmful side effects and the frequent emergence of acquired resistance are the major clinical problems. The novel platinum(IV)-based complex LA-12 exhibits a high efficacy against cancer cell lines, including cisplatin-insensitive cells, but the mechanisms by which LA-12 perturbs cell growth are unclear. We tested the effects of LA-12 on the p53 response and demonstrate that LA-12 induces unique changes in the profile of gene expression compared with cisplatin and doxorubicin. Furthermore, the ability of LA-12 to disrupt cellular proliferation is greatly enhanced by the expression of p53 and p53/47 indicating both p53-dependent and p53-independent effects of LA-12. Exposure of the human cancer cell lines H1299, A2780, BT549 and BT474 to LA-12 alters the expression of p53 and p53/47 in both a time-dependent and dose-dependent manner. Treatment of cells with a low concentration of the drug results in accumulation of p53 and p53/47 concomitant with their posttranslational modification, whereas a high dose results in the disappearance of both the forms of p53. The distinct p53 activation profile of LA-12 compared with cisplatin and doxorubicin provides a molecular explanation for the ability of this drug to treat cisplatin-resistant cells and indicates its potential usefulness as an alternative antitumour agent in first-line therapy or as a second-line therapy in patients with acquired cisplatin resistance. Anti-Cancer Drugs 19:369-379 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
ER -
HRSTKA, Roman, Darren J POWELL, Veronika KVARDOVA, Eva ROUBALOVÁ, Karima BOUROUGAA, Marco M CANDEIAS, Petr SOVA, Frantisek ZAK, Robin FAHRAEUS a Bořivoj VOJTĚŠEK. The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatin. \textit{ANTI-CANCER DRUGS}. PHILADELPHIA: LIPPINCOTT WILLIAMS \&{}amp; WILKINS, 2008, roč.~19, č.~4, s.~369-379. ISSN~0959-4973.
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