Olive (Olea europaea) Leaf Extract Induces Apoptosis and Monocyte/Macrophage Differentiation in Human Chronic Myelogenous Leukemia K562 Cells: Insight into the Underlying Mechanism

Abstract

Differentiation therapy is an attractive approach aiming at reversing malignancy and reactivating endogenous differentiation programs in cancer cells. Olive leaf extract, known for its antioxidant activity, has been demonstrated to induce apoptosis in several cancer cells. However, its differentiation inducing properties and the mechanisms involved are still poorly understood. In this study, we investigated the effect of Chemlali Olive Leaf Extract (COLE) for its potential differentiation inducing effect on multipotent leukemia K562 cells. Results showed that COLE inhibits K562 cells proliferation and arrests the cell cycle at G0/G1, and then at G2/M phase over treatment time. Further analysis revealed that COLE induces apoptosis and differentiation of K562 cells toward the monocyte lineage. Microarray analysis was conducted to investigate the underlying mechanism of COLE differentiation inducing effect. The differentially expressed genes such as IFI16, EGR1, NFYA, FOXP1, CXCL2, CXCL3, and CXCL8 confirmed the commitment of K562 cells to the monocyte/macrophage lineage. Thus our results provide evidence that, in addition to apoptosis, induction of differentiation is one of the possible therapeutic effects of olive leaf in cancer cells.

Bioavailability of Bioactive Molecules from Olive Leaf Extracts and its Functional Value

“…Despite the fact that previous research has already tested the anti-proliferative and/or cell killing abilities of different olive leaf extracts against leukemia cells (Abaza et al, 2007;Fares et al, 2011;Samet et al, 2014), none of them has proved whether the extracts maintained their anticancer properties once they entered the gastrointestinal tract. Therefore, olive leaf extracts warrant further investigation into their potential antileukemic benefits.…”

A review: benefit and bioactive properties of olive (Olea europaea L.) leaves

“…Several studies have shown that olive leaf extract exhibits a large spectrum of in vitro and in vivo properties, including antioxidant activity [85,86], radio-protective effects [85], anti-proliferative effect on leukemia cells by inducing apoptosis [39,57,87,88], cytotoxic activity against human breast cancer cells [47,89], anti-HIV virus effect [90], antifungal activity [91], gastroprotective activities [92], attenuation of diabetic neuropathic pain [93] and amelioration of gentamicin nephrotoxicity [94]. Several biological properties such as antioxidant, anti-atherosclerotic, hypoglycemic and cardioprotective effects of olive leaves have been reviewed in the literature [76,82].…”

Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human hematopoietic stem cell differentiation towards erythroid lineage

“…In order to evaluate the effect of the combination of these three compounds, cells were also treated with combination (comb) of Olp, Api7G and Lut7G at 55 mM, 5 mM, and 5 mM, respectively. The concentrations of the compounds in the mixture were determined based on the HPLC analysis of the ethanol extract of olive leaf and the compounds' effective concentration for the induction of differentiation of human chronic myelogenous leukemia K562 cells in our previous study (Samet et al, 2014a).…”

“…Olive leaves contain many bioactive compounds that have antioxidant, anti-microbial, antihypertensive, anti-viral, anti-inflammatory, hypoglycemic, neuroprotective, and anti-cancer properties (Kontogianni and Gerothanassis, 2012;Pereira et al, 2007;Somova et al, 2003;Micol et al, 2005;Wainstein et al, 2012;Seddik et al, 2011;Bouallagui et al, 2011). Olive leaf extract and compounds, such as apigenin 7-glucoside, showed anti-leukemia effects by inducing the differentiation of different leukemia cell lines (Abaza et al, 2007;Samet et al, 2014a;Tsolmon et al, 2011). While myeloid leukemia cell lines are frequently used to study differentiation of myeloid cells, these cells have a highly abnormal karyotype and often display functional differences from their normal myeloid counterparts (Choi et al, 2009).…”