Doxorubicin (DOX) is one of the most used chemotherapeutic agents in the treatment of various types of cancer. However, a continual problem that is associated with its application in therapeutic regimens is the development of dose-dependent cardiotoxicity. The progression of this process is associated with a range of different mechanisms, but especially with the high level of oxidative stress. The aim of the study was to evaluate the effects of the water and methanol-water extracts from the plant Centaurea castriferrei (CAS) obtained by the ultrasound-assisted extraction method on the DOX-induced cardiotoxicity in the rat embryonic cardiomyocyte cell line H9c2. The H9c2 cells were treated for 48 h with the DOX and water or methanol-water extracts, or a combination (DOX + CAS H2O/CAS MeOH). The MTT assay, cell cycle analysis, and apoptosis detection revealed that both the tested extracts significantly abolished the cytotoxic effect caused by DOX. Moreover, the detection of oxidative stress by the CellROX reagent, the evaluation of the number of AP sites, and the expressions of the genes related to the oxidative stress defense showed substantial reductions in the oxidative stress levels in the H9c2 cells treated with the combination of DOX and CAS H2O/CAS MeOH compared with the DOX administered alone. The tested extracts did not affect the cytotoxic effect of DOX on the MCF-7 breast cancer cell line. The obtained results constitute the basis for further research in the context of the application of C. castriferrei extracts as adjuvants in the therapy regiments of cancer patients treated with DOX.
Keywords: Asteraceae; Centaurea castriferrei Borbás & Waisb; cardiomyocytes; cardiotoxicity; doxorubicin.