Proprietary crown ethers reverse multidrug resistance and affect mitochondrial function in cancer cells (CROSBI ID 675453)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Mioč, Marija ; Marjanović, Marko ; Guberović, Iva ; Kralj, Marijeta
engleski
Proprietary crown ethers reverse multidrug resistance and affect mitochondrial function in cancer cells
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.
Multidrug resistance ; ABC transporters ; Crown ethers
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Podaci o prilogu
63-63.
2018.
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objavljeno
Podaci o matičnoj publikaciji
Libri oncologici : Croatian journal of oncology
Ozretić, Petar ; Levanat, Sonja
Zagreb: Klinički bolnički centar Sestre milosrdnice
0300-8142
2584-3826
Podaci o skupu
5th Meeting of the Croatian Association for Cancer Research with International Participation: Translating Science to Medicine "Targets and Therapeutics" (HDIR-5)
poster
08.11.2018-10.11.2018
Zagreb, Hrvatska
Povezanost rada
Biologija, Interdisciplinarne prirodne znanosti, Kemija