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@article{1202080,
author = {Vondálová Blanářová, Olga and Jelínková, Iva and Hyršlová Vaculová, Alena and Sova, P. and Hofmanová, Jiřina and Kozubík, Alois},
article_number = {6},
doi = {http://dx.doi.org/10.1111/cpr.12061},
keywords = {COLORECTAL-CANCER; DNA-DAMAGE; MITOTIC CATASTROPHE; INDUCED APOPTOSIS; CYCLE ARREST; IN-VITRO; P53; CISPLATIN; ADAMANTYLAMINE; RESISTANCE},
language = {eng},
issn = {0960-7722},
journal = {Cell Proliferation},
title = {Higher anti-tumour efficacy of platinum(IV) complex LA-12 is associated with its ability to bypass M-phase entry block induced in oxaliplatin-treated human colon cancer cells},
volume = {46},
year = {2013}
}
TY - JOUR
ID - 1202080
AU - Vondálová Blanářová, Olga - Jelínková, Iva - Hyršlová Vaculová, Alena - Sova, P. - Hofmanová, Jiřina - Kozubík, Alois
PY - 2013
TI - Higher anti-tumour efficacy of platinum(IV) complex LA-12 is associated with its ability to bypass M-phase entry block induced in oxaliplatin-treated human colon cancer cells
JF - Cell Proliferation
VL - 46
IS - 6
SP - 665-676
EP - 665-676
SN - 09607722
KW - COLORECTAL-CANCER
KW - DNA-DAMAGE
KW - MITOTIC CATASTROPHE
KW - INDUCED APOPTOSIS
KW - CYCLE ARREST
KW - IN-VITRO
KW - P53
KW - CISPLATIN
KW - ADAMANTYLAMINE
KW - RESISTANCE
N2 - ObjectivesTherapeutic potential of conventionally used platinum-based drugs in treatment of colorectal tumours has been limited due to high incidence of tumour resistance to them and to their severe side effects. This evokes a search for more suitable anti-cancer drugs. We have compared ability of oxaliplatin and a novel platinum(IV) complex, LA-12, to modulate the cell cycle and induce apoptosis in human colon adenocarcinoma HCT116 wt and p53/p21 null cells, and have investigated molecular mechanisms involved. Materials and methodsCell cycle-related changes were analysed by flow cytometry (bromodeoxyuridine/propidium iodide staining, histone H3 phosphorylation). Apoptosis was detected using flow cytometry (assays monitoring caspase activity) and fluorescence microscopy (nuclear morphology). Changes in levels of genes/proteins involved in cell cycle and apoptosis regulation were examined by RT-PCR and western blotting. ResultsOur results highlight the outstanding ability of LA-12 to induce effective elimination of colon cancer cells independently of p53/p21, and in significantly lower doses compared to oxaliplatin. While oxaliplatin induced p53- and p21-dependent G(2)-phase arrest associated with downregulation of cyclin B1 and Cdk1, LA-12 allowed cells to enter M-phase of the cell cycle regardless of p53/p21 status. ConclusionsHigher malignant cell toxicity and ability to bypass cell cycle arrest important for the cell damage repair suggest LA-12 to be a more effective candidate for elimination of colon tumours from a variety of genetic backgrounds, compared with oxaliplatin.
ER -
VONDÁLOVÁ BLANÁŘOVÁ, Olga, Iva JELÍNKOVÁ, Alena HYRŠLOVÁ VACULOVÁ, P. SOVA, Jiřina HOFMANOVÁ a Alois KOZUBÍK. Higher anti-tumour efficacy of platinum(IV) complex LA-12 is associated with its ability to bypass M-phase entry block induced in oxaliplatin-treated human colon cancer cells. \textit{Cell Proliferation}. 2013, roč.~46, č.~6, s.~665-676. ISSN~0960-7722. Dostupné z: https://dx.doi.org/10.1111/cpr.12061.
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