title: 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.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Imen
authors.identifier: 0000-0002-9865-4023
authors.initials: I
authors.lastname: Samet
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan ; Alliance of Research on North Africa, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.affiliation: Laboratory of Environmental Bioprocesses, Biotechnology Center of Sfax, Sfax 3018, Tunisia.
authors.forename: Lobna
authors.initials: L
authors.lastname: Jlaiel
authors.affiliation: Laboratory of Environmental Bioprocesses, Biotechnology Center of Sfax, Sfax 3018, Tunisia.
authors.forename: Sami
authors.initials: S
authors.lastname: Sayadi
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan ; Alliance of Research on North Africa, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D031658:Olea / Q000737:chemistry* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts