PMID- 24803988 OWN - NLM STAT- MEDLINE DCOM- 20141228 LR - 20211021 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2014 DP - 2014 TI - Olive (Olea europaea) leaf extract induces apoptosis and monocyte/macrophage differentiation in human chronic myelogenous leukemia K562 cells: insight into the underlying mechanism. PG - 927619 LID - 10.1155/2014/927619 [doi] LID - 927619 AB - 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. FAU - Samet, Imen AU - Samet I AUID- ORCID: 0000-0002-9865-4023 AD - Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan. FAU - Han, Junkyu AU - Han J AD - 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. FAU - Jlaiel, Lobna AU - Jlaiel L AD - Laboratory of Environmental Bioprocesses, Biotechnology Center of Sfax, Sfax 3018, Tunisia. FAU - Sayadi, Sami AU - Sayadi S AD - Laboratory of Environmental Bioprocesses, Biotechnology Center of Sfax, Sfax 3018, Tunisia. FAU - Isoda, Hiroko AU - Isoda H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140406 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Antineoplastic Agents) RN - 0 (Plant Extracts) SB - IM MH - Antineoplastic Agents/pharmacology MH - Apoptosis/*drug effects MH - Cell Cycle Checkpoints/drug effects MH - Cell Differentiation/*drug effects MH - Cell Proliferation/drug effects MH - Chromatography, High Pressure Liquid MH - Humans MH - K562 Cells MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism/pathology MH - Monocytes/cytology/drug effects MH - Olea/*chemistry/metabolism MH - Plant Extracts/chemistry/*pharmacology MH - Plant Leaves/chemistry/metabolism MH - Transcriptome/drug effects PMC - PMC3997986 EDAT- 2014/05/08 06:00 MHDA- 2014/12/30 06:00 PMCR- 2014/04/06 CRDT- 2014/05/08 06:00 PHST- 2013/12/06 00:00 [received] PHST- 2014/02/16 00:00 [accepted] PHST- 2014/05/08 06:00 [entrez] PHST- 2014/05/08 06:00 [pubmed] PHST- 2014/12/30 06:00 [medline] PHST- 2014/04/06 00:00 [pmc-release] AID - 10.1155/2014/927619 [doi] PST - ppublish SO - Oxid Med Cell Longev. 2014;2014:927619. doi: 10.1155/2014/927619. Epub 2014 Apr 6.