Naslov
Proprietary crown ethers reverse multidrug resistance and affect mitochondrial function in cancer cells

Autori
Mioč, Marija ; Marjanović, Marko ; Guberović, Iva ; Kralj, Marijeta

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Translating Science of Medicine - Targets and Therapeutics, Fifth Meeting of the Croatian Association for Cancer Research with International Participation : Poster presentations, in Libri oncologici, Vol. 46 No. Supplement 1 / Ozretić, Petar ; Levanat, Sonja - Zagreb : Klinički bolnički centar Sestre milosrdnice, 2018, 63-63

Skup
5th Meeting of the Croatian Association for Cancer Research with International Participation: Translating Science to Medicine "Targets and Therapeutics" (HDIR-5)

Mjesto i datum
Zagreb, Hrvatska, 08.11.2018. - 10.11.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Multidrug resistance ; ABC transporters ; Crown ethers

Sažetak
Multidrug resistance (MDR) is a known characteristic of many cancers and is a major cause of failure of chemotherapy treatments. Various cellular pathways are responsible for this phenomenon, including overexpression of ATP binding cassette (ABC) transporters called ABCB1 (MDR1/P-glycoprotein) and ABCG2 (BCRP) by cancer cells, which makes this group of proteins a valuable target for cancer therapy by reversal of MDR. Salinomycin, naturally occurring potassium (K+) ionophore, was shown to inhibit P-gp transporter and to reverse MDR effectively. Salinomycin is a K+/H+ exchanger that can affect cation transport across different cellular membranes and thus impact on membranes’ bioenergetic performance, including mitochondrial membrane polarization and function. Based on the above-mentioned studies and anticancer activity of crown-ethers that act as K+ ionophores (previously published by our group), we showed that these compounds exhibit inhibitory effect towards ABC transporters, disrupt the potassium transport and modulate mitochondrial membrane transport. In this study, we showed the effect of adamantane- substituted monoaza- and diaza-18- crown-6 ether compounds on MDR reversal and their effect on mitochondrial membrane function, depending on their lipophilicity as well as on the chemical structure of the linker to adamantane moiety. Compounds that showed as the most potent P-gp and ABCG2 inhibitors were able to sensitize cancer cells to conventional chemotherapeutics paclitaxel and mitoxantrone, the substrates of P-gp and ABCG2 transporters, respectively. These data are promising and demonstrate a potential use of crown ethers in cancer therapy, by their ability to reverse MDR.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Interdisciplinarne prirodne znanosti

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