The novel platinum(IV) complex LA-12 induces p53 and p53/47
responses that differ from the related drug, cisplatin

J 2008

The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatin

HRSTKA, Roman; Darren J POWELL; Veronika KVARDOVA; Eva ROUBALOVÁ; Karima BOUROUGAA et al.

Základní údaje

Originální název

The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatin

Autoři

HRSTKA, Roman; Darren J POWELL; Veronika KVARDOVA; Eva ROUBALOVÁ; Karima BOUROUGAA; Marco M CANDEIAS; Petr SOVA; Frantisek ZAK; Robin FAHRAEUS a Bořivoj VOJTĚŠEK

Vydání

ANTI-CANCER DRUGS, PHILADELPHIA, LIPPINCOTT WILLIAMS & WILKINS, 2008, 0959-4973

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 2.358

Označené pro přenos do RIV

UT WoS

000254247000005

Klíčová slova anglicky

cisplatin; LA-12; p53; p53/47

Změněno: 21. 2. 2013 14:52, RNDr. Eva Roubalová, Ph.D.

Anotace

V originále

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.

Citovat

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.

@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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