Quercetin Mitigates Neurotoxicity and Enhances Antileukemic Effects of Vincristine Against Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells

Acute lymphoblastic leukemia (ALL), the predominant form of childhood blood cancer, impacts roughly 60,000 children and results in approximately 25,000 deaths annually in the world. Vincristine, a chemotherapy drug widely used in the treatment of ALL, can cause neurotoxic side effects. The neurotoxic side effects and the development of drug resistance associated with vincristine can compromise the quality of life for patients. The significant side effects associated with chemotherapy drugs drive researchers and clinicians to seek plant-based compounds with minimal to no adverse effects. My study investigates how quercetin, a naturally occurring flavonoid, can mitigate vincristine-induced neurotoxicity and enhance its therapeutic effect on the survival of human acute lymphoblastic leukemia cells (CCRF-CEM cells). Vincristine (0.02, 0.2, 2 μM) and quercetin (25, 50, 75 μM) treatments exhibited a dose- and time-dependent reduction in CCRF-CEM cell proliferation over 24-72 hours. Co-treatment with quercetin (12.5, 25, 50 μM) and vincristine doses (0.01, 0.1, 1 μM) demonstrated enhanced suppression compared to vincristine alone. This combination displayed strong synergism (combination index of 0.44), emphasizing its superior efficacy in reducing leukemia cell viability. Particularly, the 0.1 μM vincristine and 25 μM quercetin combination exhibited heightened suppression of CCRF-CEM cells. My research outcomes demonstrated that quercetin significantly elevated the levels of nuclear factor erythroid 2-related factor-2 (Nrf2) expression relative to the vincristine-treated control group. This indicates a potential mechanism through which quercetin mitigates neurotoxicity and enhances the therapeutic efficacy of vincristine in the treatment of acute lymphoblastic leukemia.