Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00461337" target="_blank" >RIV/61388963:_____/16:00461337 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.18632/oncotarget.7006" target="_blank" >http://dx.doi.org/10.18632/oncotarget.7006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.7006" target="_blank" >10.18632/oncotarget.7006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1

Popis výsledku v původním jazyce

Human papillomavirus (HPV) is responsible for cervical cancer, and its role in head and neck carcinoma has been reported. No drug is approved for the treatment of HPV-related diseases but cidofovir (CDV) exhibits selective antiproliferative activity. In this study, we analyzed the effects of CDV-resistance (CDVR) in two HPV(+) (SiHa(CDV) and HeLaCDV) and one HPV(-) (HaCaT(CDV)) tumor cell lines. Quantification of CDV metabolites and analysis of the sensitivity profile to chemotherapeutics was performed. Transporters expression related to multidrug-resistance (MRP2, P-gp, BCRP) was also investigated. Alterations of CDV metabolism in SiHa(CDV) and HeLaCDV, but not in HaCaTCDV, emerged via impairment of UMP/CMPK1 activity. Mutations (P64T and R134M) as well as down-regulation of UMP/CMPK1 expression were observed in SiHa(CDV) and HeLaCDV, respectively. Altered transporters expression in SiHa(CDV) and/or HeLaCDV, but not in HaCaTCDV, was also noted. Taken together, these results indicate that CDVR in HPV(+) tumor cells is a multifactorial process.

Název v anglickém jazyce

Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1

Popis výsledku anglicky

Human papillomavirus (HPV) is responsible for cervical cancer, and its role in head and neck carcinoma has been reported. No drug is approved for the treatment of HPV-related diseases but cidofovir (CDV) exhibits selective antiproliferative activity. In this study, we analyzed the effects of CDV-resistance (CDVR) in two HPV(+) (SiHa(CDV) and HeLaCDV) and one HPV(-) (HaCaT(CDV)) tumor cell lines. Quantification of CDV metabolites and analysis of the sensitivity profile to chemotherapeutics was performed. Transporters expression related to multidrug-resistance (MRP2, P-gp, BCRP) was also investigated. Alterations of CDV metabolism in SiHa(CDV) and HeLaCDV, but not in HaCaTCDV, emerged via impairment of UMP/CMPK1 activity. Mutations (P64T and R134M) as well as down-regulation of UMP/CMPK1 expression were observed in SiHa(CDV) and HeLaCDV, respectively. Altered transporters expression in SiHa(CDV) and/or HeLaCDV, but not in HaCaTCDV, was also noted. Taken together, these results indicate that CDVR in HPV(+) tumor cells is a multifactorial process.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CC - Organická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GA14-00522S" target="_blank" >GA14-00522S: Syntézy nových prolékových forem biologicky aktivních nukleotidových analogů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

OncoTarget

ISSN

1949-2553

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

10386-10401

Kód UT WoS článku

000375672900058

EID výsledku v databázi Scopus

2-s2.0-84961674882