Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells
The result's identifiers
Result code in 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>
Alternative codes found
RIV/67985858:_____/15:00448145 RIV/00209805:_____/15:#0000633
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CA - Inorganic chemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Investigational New Drugs
ISSN
0167-6997
e-ISSN
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Volume of the periodical
33
Issue of the periodical within the volume
5
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
10
Pages from-to
1123-1132
UT code for WoS article
000364972700015
EID of the result in the Scopus database
2-s2.0-84942198422