Interaction of adenosine, modified using carborane clusters, with ovarian cancer cells: A new anticancer approach against chemoresistance

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388980%3A_____%2F21%3A00544526" target="_blank" >RIV/61388980:_____/21:00544526 - isvavai.cz</a>

Výsledek na webu

<a href="http://hdl.handle.net/11104/0321368" target="_blank" >http://hdl.handle.net/11104/0321368</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13153855" target="_blank" >10.3390/cancers13153855</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interaction of adenosine, modified using carborane clusters, with ovarian cancer cells: A new anticancer approach against chemoresistance

Popis výsledku v původním jazyce

Platinum compounds remain the first-line drugs for the treatment of most lethal gynecological malignancies and ovarian cancers. Acquired platinum resistance remains a major challenge in gynecological oncology. Considering the unique physicochemical properties of the metallacarboranes modifier and the significant role of nucleoside derivatives as anticancer antimetabolites, we designed and synthesized a set of adenosine conjugates with metallacarboranes containing iron, cobalt, or chromium as semi-abiotic compounds that influence the cisplatin sensitivity of ovarian cancer cells. Adherent cultures of ovarian carcinoma cell lines and multicellular spheroids, ranging from sensitive to highly resistant including experimental cell lines “not responding” to platinum drugs were used. Iron-containing metallacarborane conjugates showed the best anticancer activity, especially against resistant cells. Compound modified at the C2′ nucleoside position showed the best activity in resistant cancer cells and highly resistant cancer spheroids exposed to cisplatin, increasing cell cycle arrest, apoptosis or necrosis, and reactive oxygen species production. Moreover, it showed high cellular accumulation and did not induce cross-resistance to cisplatin, carboplatin, doxorubicin, paclitaxel, or gemcitabine in long-term cultures. The reference nido-carborane derivative (no metal ions) and unmodified nucleosides were not as effective. These findings indicate that metallacarborane modification of adenosine may sensitize ovarian cancer cells to cisplatin in combination treatment.

Název v anglickém jazyce

Interaction of adenosine, modified using carborane clusters, with ovarian cancer cells: A new anticancer approach against chemoresistance

Popis výsledku anglicky

Platinum compounds remain the first-line drugs for the treatment of most lethal gynecological malignancies and ovarian cancers. Acquired platinum resistance remains a major challenge in gynecological oncology. Considering the unique physicochemical properties of the metallacarboranes modifier and the significant role of nucleoside derivatives as anticancer antimetabolites, we designed and synthesized a set of adenosine conjugates with metallacarboranes containing iron, cobalt, or chromium as semi-abiotic compounds that influence the cisplatin sensitivity of ovarian cancer cells. Adherent cultures of ovarian carcinoma cell lines and multicellular spheroids, ranging from sensitive to highly resistant including experimental cell lines “not responding” to platinum drugs were used. Iron-containing metallacarborane conjugates showed the best anticancer activity, especially against resistant cells. Compound modified at the C2′ nucleoside position showed the best activity in resistant cancer cells and highly resistant cancer spheroids exposed to cisplatin, increasing cell cycle arrest, apoptosis or necrosis, and reactive oxygen species production. Moreover, it showed high cellular accumulation and did not induce cross-resistance to cisplatin, carboplatin, doxorubicin, paclitaxel, or gemcitabine in long-term cultures. The reference nido-carborane derivative (no metal ions) and unmodified nucleosides were not as effective. These findings indicate that metallacarborane modification of adenosine may sensitize ovarian cancer cells to cisplatin in combination treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/GA19-04630S" target="_blank" >GA19-04630S: Ladění elektrochemických vlastností bórových polyedrů pokročilými substitučními metodami pro použití jako biokonjugátů: systematický základní výzkum</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Cancers (Basel)

ISSN

2072-6694

e-ISSN

2072-6694

Svazek periodika

13

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

48

Strana od-do

3855

Kód UT WoS článku

000681934500001

EID výsledku v databázi Scopus

2-s2.0-85111386485