Effect of Dietary Intervention With High-Oleocanthal and Oleacin Extra Virgin Olive Oil in Patients With Chronic Lymphocytic Leukemia a Pilot Study

Extra virgin olive oil (EVOO) is the major component of the Mediterranean diet. More than 200 different chemical compounds have been detected in olive oil, including fatty acids, sterols, carotenoids, terpenoids, flavonoids, tocopherols and olive polyphenols. Virgin olive oil contains a variety of important phenolic components, mainly corresponding to the compounds tyrosol, hydroxytyrosol, oleocanthal (OC) ,oleacin (OL) ,ligstroside and oleuropein aglycones .Among these olive phenols, oleocanthal , a dialdehydic form of dicarboxymethyl ligstroside aglycone which has been isolated from EVOO, presents a wide range of biological effects including antioxidant, anti-inflammatory, anticancer, neuroprotective and antidiabetic activities and for this reason has attracted more scientific attention.

Chronic Lymphocytic Leukemia (CLL), the most commonly diagnosed adult leukemia in Western countries, is responsible for about 1 in 4 cases of all leukemias. It is characterized by the accumulation of monoclonal B-cells in bone marrow, peripheral blood, lymphatic tissues and spleen, while it is often asymptomatic and slow in its development. Patients with CLL do not always require immediate therapy. However, patients who appear symptoms have an approximate median survival range from 18 months to 6 years depending on the clinical stage. Criteria for the diagnosis of CLL are monoclonal B lymphocytes ≥5000 lymphocytes/ml in the peripheral blood for at least 3 months, prolymphocytes ≤55%, co-expression of claster of diferentiation (CD)5 and B-cell surface antigens CD 19, CD 20, and CD 23, low levels of CD 20, CD 79b and low expression of surface immunoglobulins (sIg), and kappa or lambda light chain restriction. The standard clinical procedures to estimate prognosis are the clinical staging systems developed by Rai et al and Binet et al.

The level of apoptosis in hematopoiesis may provide information about the mechanism which is responsible for the regulation of progenitor's and stem cell's proliferation. The dysfunction of apoptosis has found to be associated with leukemia. An increase in the expression of Apo-1/fas (CD 95) apoptotic marker in myeloid progenitor cells in CLL patients and a corresponding decrease in the apoptotic B-cell lymphoma 2 (BCL-2) inhibitor has been described. Recent studies showed also that the increase in CLL patients' lymphocytes may be due to the disturbed balance between the proliferation and apoptosis of CLL cells while the changes in apoptosis-related protein expression are recognized during all the stages of Binet in CLL. The p38 levels are reduced (resistance to apoptosis) and Induced myeloid leukemia cell differentiation protein (Mcl-1) and Survivin levels are elevated, so as to enhance the survival of B lymphocytes.

Survivin is a protein inhibitor of apoptosis which inhibits caspases and blocks cell death. It is highly expressed in most cancers, including hematological, and is associated with a poor clinical outcome. The apoptotic marker CD 95 (Apo-1/fas) and its ligand, CD 95 is a death receptor ligand that mediates apoptosis induction in order to maintain immune homeostasis and has the capacity to mediate apoptosis induction in cancer cells, generating an 18-kilodalton fragment termed caspase-cleaved cytokeratin-18 (cCK-18).

Oleocanthal has been shown to induce cytotoxicity and apoptosis in vitro in human acute promyelocytic leukemia and in myeloma cells. It may also cause primary necrosis and cellular apoptosis by inducing lysosomal membrane permeability in different cancer cell lines.