Repozytorium publikacji - Politechnika Gdańska

Multidrug resistance (MDR) is a process that constitutes a significant obstacle to effective anticancer therapy. Here, we examined whether unsymmetrical bisacridines (UAs) are substrates for ABC transporters and can influence their expression in human colon LS 174T and prostate DU 145 cancer cells. Moreover, we investigated the cytotoxicity and the cellular response induced by UAs in these cells. The ATPase activities of MDR1, MRP1, and MRP2 were measured using vesicles prepared from insect Sf9 cells expressing particular ABC transporters. The gene expression and protein levels were analyzed using qPCR and Western blotting. The cellular effects were studied by MTT (cytotoxicity), flow cytometry (cell cycle analysis and phosphatidylserine externalization), and fluorescence microscopy. We showed that UAs are substrates for MDR1. Importantly, they did not influence remarkably the expressions of the ABCB1, ABCC1, and ABCC2 genes and the levels of the MDR1 and PXR proteins in the studied cells. Furthermore, the cytotoxicity and the level of apoptosis triggered by UAs in LS 174T cells possessing higher expressions of metabolic enzymes were lower compared with DU 145 cells. These results indicate that during possible UA treatment, the occurrence of drug resistance could be limited, which could favor the use of such compounds as potential candidates for future studies.

Autorzy

• dr inż. Monika Pawłowska link otwiera się w nowej karcie ,
• Jolanta Kulesza link otwiera się w nowej karcie ,
• dr inż. Ewa Paluszkiewicz link otwiera się w nowej karcie ,
• dr hab. Ewa Augustin link otwiera się w nowej karcie ,
• prof. dr hab. inż. Zofia Mazerska link otwiera się w nowej karcie