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

## TL;DR

This study explores how certain compounds can help overcome drug resistance in leukemia cells by targeting a key protein involved in resistance.

## Contribution

The study identifies Apigenin, Chrysin, and Luteolin as potential agents to reverse doxorubicin resistance in leukemia cells.

## Key findings

- Apigenin, Chrysin, and Luteolin effectively overcome doxorubicin resistance in HL-60/DOXO cells.
- Berberine does not reverse resistance and may hinder doxorubicin's effectiveness.
- The effects may be due to interaction with the hyperactivated NRF2 transcription factor.

## Abstract

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.