Hesperetin increases membrane progesterone receptor expression in human myeloid leukemia cells and reduces ROS

Chronic myeloid leukemia (CML) is characterized by high levels of reactive oxygen species (ROS), which contribute to disease progression and drug resistance. In addition, membrane progesterone receptors (mPRs) may play roles in the proliferation and differentiation of leukemia cells, although their significance in CML remains underexplored. Hesperetin (Hst), a citrus flavonoid, has shown anticancer and antioxidant properties. This study aimed to investigate whether Hst affects mPR expression and ROS levels in K562 cells, to provide initial insights into its potential as a complementary approach for CML treatment. Cell viability was evaluated using an MTT test following treatment with different concentrations of Hst (60-300 µM) for 24, 48, and 72 h. Based on these results, 120 µM was selected as a moderate sub-cytotoxic concentration for evaluating mPRα and mPRβ expression and ROS levels using flow cytometry and DCFDA fluorescence. Hst reduced K562 cell viability in a time- and dose-dependent manner, with IC50 values of approximately 327 µM (24 h), 247 µM (48 h), and 213 µM (72 h). Based on these results, 120 µM Hst was used as a moderate sub-cytotoxic dose to evaluate its effects on both mPRα and mPRβ expression and ROS levels, which were significantly altered compared to untreated cells (P < 0.05). According to our results, Hst shows promising in vitro effects on K562 cells and may be considered for further preclinical research as a potential complementary agent for CML treatment.