Potential of Apigenin, Berberine, Chrysin, and Luteolin to Overcome Doxorubicin Resistance in Acute Promyelocytic Leukemia HL-60 Cells.

Multidrug resistance (MDR) is one of the leading causes of high mortality in cancer. The NRF2 (Nuclear Factor Erythroid 2-Related Factor 2) transcriptional factor can play a major role in MDR development. In this study, we tested the NRF2 inhibitors-Apigenin, Berberine, Chrysin, and Luteolin (ABCL) for their ability to overcome doxorubicin resistance in acute promyelocytic leukemia HL-60 cells (HL-60/DOXO cells). We examined the effects of NRF2 inhibitors on cell viability, apoptosis, DNA damage, and reactive oxygen species (ROS) generation. Our results indicate that Apigenin, Chrysin, and Luteolin can effectively overcome doxorubicin resistance in HL-60/DOXO cells. On the contrary, Berberine does not demonstrate this activity and even hinders doxorubicin's activity. We hypothesize that the observed effects of ABCL may result from their interaction with the NRF2 factor, which is hyperactivated in the tested HL-60/DOXO cells.