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

J 2013

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

VONDÁLOVÁ BLANÁŘOVÁ, Olga; Iva JELÍNKOVÁ; Alena HYRŠLOVÁ VACULOVÁ; P. SOVA; Jiřina HOFMANOVÁ et al.

Základní údaje

Originální název

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

Autoři

VONDÁLOVÁ BLANÁŘOVÁ, Olga; Iva JELÍNKOVÁ; Alena HYRŠLOVÁ VACULOVÁ; P. SOVA; Jiřina HOFMANOVÁ a Alois KOZUBÍK

Vydání

Cell Proliferation, 2013, 0960-7722

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.280

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/13:00082130

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1111/cpr.12061

UT WoS

000326233800007

Klíčová slova anglicky

COLORECTAL-CANCER; DNA-DAMAGE; MITOTIC CATASTROPHE; INDUCED APOPTOSIS; CYCLE ARREST; IN-VITRO; P53; CISPLATIN; ADAMANTYLAMINE; RESISTANCE

Štítky

AKR, rivok

Změněno: 27. 4. 2016 14:20, Ing. Andrea Mikešková

Anotace

V originále

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.

Návaznosti

MSM0021622430, záměr

Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Citovat

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. Cell Proliferation. 2013, roč. 46, č. 6, s. 665-676. ISSN 0960-7722. Dostupné z: https://doi.org/10.1111/cpr.12061.

@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 = {https://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://doi.org/10.1111/cpr.12061.

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