Chutiphong Jirawatpraphakorn, Dalina Tanyong, Attasak Jaree, Weerapat Owattanapanich
Abstract Acute leukemia is an aggressive hematologic malignancy with limited treatment success owing to drug resistance, severe adverse effects, and high costs. Vitexin, a natural compound, demonstrates promising anticancer properties by modulating multiple pathways and inducing apoptosis, while maintaining favorable toxicity profiles. This study examined the pro-apoptotic effects of vitexin on leukemic cell lines (NB-4 and MOLT-4) and patient-derived bone marrow cells, as well as its combined effect with daunorubicin. Cytotoxicity was evaluated using MTT, apoptosis was assessed via Annexin V/PI flow cytometry, and molecular mechanisms were elucidated through in silico bioinformatic, RT-qPCR, and Western blot analyses. Vitexin decreased cell viability in a dose- and time-dependent manner (48 hours of IC 50 : 901 µM in NB-4, 929 µM in MOLT-4), with minimal toxicity in normal PBMCs. Synergistic interaction with daunorubicin was confirmed through the combination index. Vitexin elevated apoptosis up to 42.82% by downregulating HIF-1α and upregulating caspase-3 at both transcriptional and translational levels. Patient-derived bone marrow cells, the combination treatment induced the highest apoptosis (22.15% AML, 18.82% ALL). Vitexin induces apoptosis via modulation of HIF-1α/Bcl-2/caspase-3 pathway and potentiates efficacy of daunorubicin, thereby supporting potential as an adjunctive therapeutic in acute leukemia. Further in vivo studies are necessary to elucidate pharmacokinetics and clinical applicability.