Ameliorative Effect of Lycopene and Capsaicinoid Glucoside in Acute Myeloid Leukemia

ABSTRACT Acute myeloid leukemia (AML) is a hematological malignancy with limited therapeutic efficacy, particularly in elderly and chemotherapy‐resistant patients. Although cytarabine and daunorubicin are the conventional treatments, their 5‐year survival rate is less than 15% in some populations. Nonetheless, natural bioactive substances with antileukemic properties might be a viable treatment strategy. The antileukemic potential of lycopene (Lyc) and capsaicinoid glucoside (CG), individually and in combination, is examined in this study as a possible adjuvant or alternative treatment. This study employed both in‐vitro (HL‐60 cell line) and in‐vivo (benzene‐induced leukemia rat model) methods. Cytotoxicity, apoptosis, and proliferation were evaluated in‐vitro using MTT assays, Trypan blue, crystal violet staining and flow cytometry (Annexin‐V/PI). Hematological parameters (WBC, RBC, neutrophils), oxidative stress indicators (SOD, GSH), qPCR and ELISA for anti‐apoptotic/proliferative markers (Bcl‐2, NF‐κB, Ki‐67, PCNA) were assessed in in vivo tests. To verify morphological alterations, blood smear analysis was carried out. Lyc and CG showed dose‐dependent cytotoxicity in vitro, synergistically Lyc+CG showed lowest cytotoxicity with IC 50 values of 21.35. Synergistic effects were shown by the Lyc+CG combination, which dramatically decreased cell viability and increased apoptosis (40.59% early apoptosis, 18.72% late apoptosis). In‐vitro and in‐vivo study showed that Lyc+CG reduced proliferation and anti‐apoptotic effect, restored SOD and GSH levels, and normalized haematological parameters ( p < 0.001). The Lyc+CG group's blood smears revealed more apoptotic bodies and fewer blast cells. By causing apoptosis, lowering oxidative stress, and preventing proliferation in cell line (HL‐60) and animal models (benzene‐induced leukemia in rats), the combination of Lyc and CG demonstrates strong antileukemic action. These results encourage more research into Lyc+CG as a possible AML treatment approach. To completely clarify its therapeutic potential, future research should concentrate on clinical trials and molecular insights.