“EVALUATING THE PRO-APOPTOTIC AND ANTIOXIDANT EFFECTS OF HESPERIDIN AND HESPERETIN IN LEUKEMIA CELL LINES”

Abstract

The proliferative state of cancer cells, characterized by uncontrolled division and evasion of programmed cell death, is a hallmark of malignancy. Citrus flavanones, including hesperidin (HD) and its aglycone hesperetin (HT), exhibit a spectrum of anticancer actions, ranging from antioxidant and chemopreventive to anti-inflammatory, anti-angiogenic, cytostatic, and cytotoxic effects across various cancer models. In this study, HD and HT were evaluated for their pro-apoptotic properties in K562, HL60, U937, and THP1 leukemia cell lines. HT demonstrated a substantial induction of apoptosis, with rates between 10% and 25% at 24 and 48 hours across all tested cell lines. HD showed comparable apoptotic effects in HL60 and K562 cell lines; however, in THP1 and U937 cell lines, HD-induced apoptosis was markedly lower, ranging from 5% to 8%. The impact on reactive oxygen species (ROS) generation was variable. Both HT and HD reduced ROS levels at 48 hours in HL60 and K562 cell lines, whereas in THP1 and U937 cell lines, ROS generation increased. Notably, HD consistently decreased ROS levels over the same period. Preliminary cell cycle analysis revealed that HT caused cell cycle arrest in the G2/M phase in HL60 and K562 cell lines, while HD induced arrest in the G0/G1 phase in the same cell lines. These findings suggest that HD and HT hold promise as therapeutic agents in leukemia treatment, attributed to their pro-apoptotic and cell cycle arrest capabilities. HT exhibited a higher induction of apoptosis compared to HD, highlighting its potential for greater efficacy. The differential effects on ROS generation underscore the complexity of their mechanisms of action. The distinct cell cycle arrest phases induced by HT and HD in HL60 and K562 cell lines further emphasize their complementary roles. These preliminary results advocate for continued research into HD and HT as part of a comprehensive approach to leukemia therapy, aiming to optimize therapeutic outcomes while minimizing adverse effects.