Olive Leaf Extract (OLE) Anti-Tumor Activities Against Hematologic Tumors: Potential Therapeutic Implications for Pediatric Patients with B-Acute Lymphoblastic Leukemia

<b>Background/Objectives:</b> Several studies reported that olive leaf extract (OLE) may exert potent anti-cancer activities against human solid and hematological tumors. Such effects are mostly related to the polyphenol oleuropein and its derivatives, which are highly concentrated in OLE. Here, we investigated the anti-tumor effects of OLE in vitro against human acute leukemia and lymphoma cells. <b>Methods:</b> Cell proliferation and apoptosis have been evaluated by flow cytometry (using CFSE and Annexin-V/7AAD, respectively) in the presence or absence of OLE at different concentrations and in combination with or without chemotherapeutic drugs. Cellular pathways have been analyzed using antibody arrays. <b>Results:</b> OLE inhibited cell proliferation and induced apoptosis in B-acute lymphoblastic leukemia (B-ALL) and, to a lesser extent, in lymphomas and acute myeloid leukemia (AML) cell lines. Notably, OLE-induced apoptosis also occurs in primary leukemic blasts from B-ALL patients, both at diagnosis and at relapse, but only marginally in primary AML blasts. The expression and phosphorylation of proteins involved in the induction of apoptosis were modulated by OLE in B-ALL, whereas modest effects were observed in AML. Interestingly, some proteins were modulated in opposite ways in B-ALL and AML, potentially explaining their different responses to OLE. Finally, a synergistic and additive effect was observed for OLE in combination with cytarabine, but not with cyclophosphamide. <b>Conclusions:</b> We may envisage that OLE may be used as a food supplement in B-ALL patients treated with cytarabine, taking advantage of the potentiated effect of chemotherapy, without additional side effects.