Background. The success of therapies against colon cancer is limited by the induction of reactions that promote the generation of reactive oxygen species (ROS), which in turn trigger a series of processes at the cellular level. One adverse effect of ROS is the development of drug resistance through different mechanisms. Methods. We investigated the effect of hydrogen peroxide (H2O2) on drug resistance associated with expression of the ATP-binding cassette (ABC) membrane transporters P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in wild-type HT-29 and doxorubicin-resistant HT29DxR colon cancer cells. The effect of H2O2 on ROS generation was evaluated, and the expression of Pgp and BCRP was examined using confocal microscopy. The effect of N-acetyl cysteine (NAC), an inhibitor of ROS, on the expression of ABC transporters was determined using different inducers of ROS. Results. H2O2 induced expression of transporters in HT-29 and HT-29Dx cells. NAC reduced Pgp and BCRP expression to a greater extent in HT-29DxR cells compared with HT-29 cells and non-treated cells. Co-treatment with NAC decreased the expression of ABC transporters in response to ROS inducers. Conclusions. Generation of ROS promotes the expression of ABC transporters associated with drug resistance in HT-29 colon cancer cells. Understanding the mechanism associated to multidrug resistance and ROS induction could be favor to the development of novel therapies.
|Original language||English (US)|
|Journal||Cancer Chemotherapy and Pharmacology|
|State||Unpublished - Dec 19 2018|