Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F15%3A00448145" target="_blank" >RIV/61388955:_____/15:00448145 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985858:_____/15:00448145 RIV/00209805:_____/15:#0000633

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s10637-015-0274-y" target="_blank" >http://dx.doi.org/10.1007/s10637-015-0274-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10637-015-0274-y" target="_blank" >10.1007/s10637-015-0274-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells

Popis výsledku v původním jazyce

Background Ovarian cancer is the seventh-most common cancer amongst women and the most deadly gynecologic cancer. Cisplatin based drugs are used in first line therapy, but resistance represents a major obstacle for successful treatment. In this study, we investigated the anticancer effects and mechanism of action of three titanocene difluorides, two bearing a pendant carbohydrate moiety (alpha-D-ribofuranos-5-yl) on their periphery and one without any substitution. Results The efficacy of these compounds on ovarian cancer cell lines was evaluated in relation to their particular chemical structure and compared with cisplatin as the most common treatment modality for this type of cancer. The typical mechanism of cisplatin action involves DNA damage, activation of p53 protein and induction of cell death, as previously described for titanium ions. Nevertheless, our data indicate that the effect of titanocene difluoride derivatives is mediated via the endoplasmic reticulum stress pathway and autophagy. Conclusion We anticipate that the presence of substituents on cyclopentadienyl ring(s) might play an important role in modulation of the activity of particular compounds. Titanocene difluorides exert comparable cytotoxic activity as cisplatin and are more efficient in cisplatin-resistant cell lines. Our results suggest potential utilization of these compounds especially in the treatment of cisplatin-resistant tumor cells.

Název v anglickém jazyce

Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells

Popis výsledku anglicky

Background Ovarian cancer is the seventh-most common cancer amongst women and the most deadly gynecologic cancer. Cisplatin based drugs are used in first line therapy, but resistance represents a major obstacle for successful treatment. In this study, we investigated the anticancer effects and mechanism of action of three titanocene difluorides, two bearing a pendant carbohydrate moiety (alpha-D-ribofuranos-5-yl) on their periphery and one without any substitution. Results The efficacy of these compounds on ovarian cancer cell lines was evaluated in relation to their particular chemical structure and compared with cisplatin as the most common treatment modality for this type of cancer. The typical mechanism of cisplatin action involves DNA damage, activation of p53 protein and induction of cell death, as previously described for titanium ions. Nevertheless, our data indicate that the effect of titanocene difluoride derivatives is mediated via the endoplasmic reticulum stress pathway and autophagy. Conclusion We anticipate that the presence of substituents on cyclopentadienyl ring(s) might play an important role in modulation of the activity of particular compounds. Titanocene difluorides exert comparable cytotoxic activity as cisplatin and are more efficient in cisplatin-resistant cell lines. Our results suggest potential utilization of these compounds especially in the treatment of cisplatin-resistant tumor cells.

Druh

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

CEP obor

CA - Anorganická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Investigational New Drugs

ISSN

0167-6997

e-ISSN

—

Svazek periodika

33

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

1123-1132

Kód UT WoS článku

000364972700015

EID výsledku v databázi Scopus

2-s2.0-84942198422