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

Table 3

Changes in gene expression profile induced by treatment Of K562 cells with Chemlali Olive Leaf Extract (COLE).

Gene symbol	Gene title	Accession number	Molecular function/biological process	Gene expression (treatment/control)
				100 µg/mL		150 µg/mL
				Fold change	𝑃 value	Fold change	𝑃 value
CHEK2	CHK2 checkpoint homolog (S. pombe)	NM_001005735; /// NM_007194; /// NM_145862	Cell cycle, kinase activity	1.702	1.03𝐸−02	1.620	1.44𝐸−02
CDC25C	Cell division cycle 25 homolog C (S. pombe)	NM_001790 ///; NM_022809	Cell cycle, regulation of cyclin-dependent protein kinase activity	−1.452	3.98𝐸−02	−1.553	2.40𝐸−02
CDC25A	Cell division cycle 25 homolog A (S. pombe)	NM_001789 ///; NM_201567	Phosphoprotein phosphatase activity, regulation of cyclin-dependent protein kinase activity	2.284	8.1𝐸−03	2.324	7.60𝐸−03
CASP6	Caspase 6, apoptosis-related cysteine peptidase	NM_001226 ///; NM_032992	Positive regulation of apoptosis, acute inflammatory response to nonantigenic stimulus, apoptosis, hydrolase activity, induction of apoptosis, proteolysis, and peptidase activity	1.705	3.64𝐸−02	1.779	2.88𝐸−02
DFFA	DNA fragmentation factor, 45 kDa, alpha polypeptide	NM_004401 ///; NM_213566	Apoptosis, induction of apoptosis, caspase-activated deoxyribonuclease activity, DNA fragmentation involved in apoptosis, positive regulation of apoptosis, and negative regulation of apoptosis	2.678	1.30𝐸−02	1.967	4.30𝐸−02
BID	BH3 interacting domain death agonist	NM_001196 ///; NM_197966 ///; NM_197967	Positive regulation of apoptosis, death receptor binding, release of cytochrome c from mitochondria, activation of proapoptotic gene products, and regulation of mitochondrial membrane permeability	1.644	3.46𝐸−02	1.577	4.48𝐸−02
CASP8	Caspase 8, apoptosis-related cysteine peptidase	NM_001080124; ///; NM_001080125; /// NM_001228; /// NM_033355; /// NM_033356; /// NM_0	Peptidase activity, proteolysis, apoptosis, regulation of apoptosis, positive regulation of I-kappaB kinase-NF-kappaB cascade, activation of proapoptotic gene products, induction of apoptosis by extracellular signals, and macrophage differentiation	1.310	1.3𝐸−01	1.633	2.63𝐸−02
IGF1R	Insulin-like growth factor 1 receptor	NM_000875	Positive regulation of proliferation, positive regulation of migration, and antiapoptosis	−2.397	3.09𝐸−02	−3.312	1.10𝐸−02
HSPA5	Heat shock 70 kDa protein 5	NM_005347	Negative regulation of caspase activity, caspase inhibitor activity	−1.790	2.10𝐸−03	−2.454	0.4𝐸−03
BCL2	B cell CLL/lymphoma 2	NM_000633 ///; NM_000657	Activation of proapoptotic gene products, negative regulation of myeloid cell apoptosis, regulation of programmed cell death, and negative regulation of mitotic cell cycle	−1.782	1.13𝐸−02	−1.804	1.05𝐸−02
FECH	Ferrochelatase	NM_000140 ///; NM_001012515	Erythrocyte differentiation	−1.657	3.60𝐸−02	−1.975	1.38𝐸−02
GYPA	Glycophorin A (MNS blood group)	NM_002099	Erythrocyte differentiation	−3.823	8.40𝐸−03	−4.227	6.5𝐸−03
HBE1	Hemoglobin, epsilon 1	NM_005330	Erythrocyte differentiation	−2.678	2.30𝐸−02	−3.419	1.10𝐸−02
NFE2	Nuclear factor (erythroid-derived 2), 45 kDa	NM_001136023; /// NM_006163	Regulation of transcription, cell-cell signaling, and megakaryocyte differentiation	−1.611	2.12𝐸−01	−1.366	3.86𝐸−01
TUBB1	Tubulin, beta 1	NM_030773	Microtubule-based process	−1.565	7.53𝐸−02	−1.4501	1.18𝐸−01
BACH2	BTB and CNC homology 1, basic leucine zipper transcription factor 2	NM_001170794; /// NM_021813	Regulation of transcription, DNA dependent	−1.569	1.21𝐸−02	−1.798	0.47𝐸−02
ACIN1	Apoptotic chromatin condensation inducer 1	NM_001164814; ///; NM_001164815; ///; NM_001164816; ///; NM_001164817; /// NM_014977	Positive regulation of monocyte differentiation, apoptosis, apoptotic chromosome condensation, and ATPase activity	1.403	3.65𝐸−02	1.669	9.47𝐸−03
IFI16	Interferon, gamma-inducible protein 16	NM_005531	Monocyte differentiation, myeloid cell differentiation, regulation of transcription, DNA dependent, DNA damage response, and cell proliferation	1.400	4.75𝐸−02	2.186	2.80𝐸−03
EGR1	Early growth response 1	NM_001964	Transcription factor activity, regulation of transcription, DNA dependent	1.441	1.11𝐸−01	1.765	3.38𝐸−02
NFYA	Nuclear transcription factor Y, alpha	NM_002505 ///; NM_021705	Transcription factor activity	1.916	0.95𝐸−03	1.729	1.85𝐸−03
FOXP1	Forkhead box P1	NM_001012505; /// NM_032682	Negative regulation of transcription, transcription repressor activity	−1.376	3.91𝐸−02	−1.552	0.0141
IL8	Interleukin-8	NM_000584	Immune response, neutrophil chemotaxis, regulation of cell adhesion, neutrophil activation, negative regulation of cell proliferation, cell cycle arrest, inflammatory response, and chemotaxis	1.015	9.62𝐸−01	3.638	1.46𝐸−02
CXCL2	Chemokine (C-X-C motif) ligand 2	NM_002089	Neutrophil chemotaxis, immune response, inflammatory response, and chemotaxis	1.559	1.71𝐸−01	5.831	2.74𝐸−03
CXCL3	Chemokine (C-X-C motif) ligand 3	NM_002090	Neutrophil chemotaxis, immune response, inflammatory response, chemotaxis, and leukocyte chemotaxis	1.447	2.75𝐸−01	5.181	4.94𝐸−03
NUP85	Nucleoporin 85 kDa	NM_024844	Macrophage chemotaxis, cytokine-mediated signaling pathway, and chemotaxis	1.740	0.54𝐸−02	1.636	8.33𝐸−03
AP1G1	Adaptor-related protein complex 1, gamma 1 subunit	NM_001030007; /// NM_001128	Microtubule cytoskeleton organization, intracellular protein transport, endocytosis, and vesicle mediated transport	1.543	0.58𝐸−02	1.547	5.69𝐸−03
CTNNB1	Catenin (cadherin-associated protein), beta 1, 88 kDa	NM_001098209; ///; NM_001098210; /// NM_001904	Wnt receptor signaling pathway through beta-catenin, cell morphogenesis involved in differentiation, regulation of transcription, regulation of cell differentiation, cadherin, positive regulation of MAPKKK cascade, cell-cell adhesion, cell-matrix adhesion, regulation of cell adhesion, hemopoiesis, and so forth	1.449	1.29𝐸−02	1.530	8.09𝐸−03
ICAM3	Intercellular adhesion molecule 3	NM_002162	Cell-cell adhesion, integrin binding	1.841	3.0𝐸−03	1.775	3.76𝐸−03
PNN	Pinin, desmosome associated protein	NM_002687	Cell-cell adhesion, negative regulation of cell cycle	1.746	1.43𝐸−02	2.061	5.79𝐸−03
HSPB11	Heat shock protein family B (small), member 11	NM_016126	Cell adhesion	1.640	0.48𝐸−02	1.709	3.58𝐸−03
RAB21	RAB21, member RAS oncogene family	NM_014999	Protein transport, endocytosis	1.559	0.37𝐸−02	1.605	2.95𝐸−03
RAB5C	RAB5C, member RAS oncogene family	NM_004583 ///; NM_201434	Protein transport, endocytosis	1.821	1.10𝐸−02	1.844	1.03𝐸−02
RAB11A	RAB11A, member RAS oncogene family	NM_004663	Protein transport, endocytosis	1.861	1.98𝐸−02	1.964	1.51𝐸−02
MAP3K2	Mitogen-activated protein kinase kinase kinase 2	NM_006609	Activation of MAPK activity, activation of JUN kinase activity, cell proliferation, and protein amino acid phosphorylation	1.290	2.04𝐸−01	1.956	1.63𝐸−02
MAP3K5	Mitogen-activated protein kinase kinase kinase 5	NM_005923	MAPKKK cascade, activation of JUN kinase activity, protein amino acid phosphorylation, activation of MAPK activity, and apoptosis	1.836	0.52𝐸−02	1.554	1.59𝐸−02
MAP3K7	Mitogen-activated protein kinase kinase kinase 7	NM_003188 ///; NM_145331 ///; NM_145332 ///; NM_145333	I-kappaB phosphorylation, activation of NF-kappaB-inducing kinase activity, MAPKKK cascade, positive regulation of JNK cascade, T cell receptor signaling pathway, negative regulation of apoptosis, and regulation of interleukin-2 production	1.423	2.41𝐸−02	1.575	1.04𝐸−02
TRAF6	TNF receptor-associated factor 6	NM_004620 ///; NM_145803	Positive regulation of interleukin-12 biosynthetic process, regulation of apoptosis, protein polyubiquitination, T cell receptor signaling pathway, and positive regulation of I-kappaB kinase-NF-kappaB cascade	1.409	3.10𝐸−02	1.506	1.76𝐸−02
NFKB1	Nuclear factor of kappa light polypeptide gene enhancer in B cells 1	NM_001165412; /// NM_003998	Inflammatory response, regulation of transcription, apoptosis, regulation of lipid metabolic process, and positive regulation of foam cell differentiation	1.498	0.11𝐸−02	1.695	0.42𝐸−03
SNIP1	Smad nuclear interacting protein 1	NM_024700	Regulation of transcription, insulin receptor signaling pathway, and I-kappaB kinase-NF-kappaB cascade	1.683	3.09𝐸−02	1.828	1.94𝐸−02
MAPK14	Mitogen-activated protein kinase 14	NM_001315 ///; NM_139012 ///; NM_139013 ///; NM_139014	Stress-activated MAPK cascade, cell surface receptor linked signal transduction, skeletal muscle tissue development, Ras protein signal transduction, response to stress, angiogenesis, and so forth	−1.468	1.52𝐸−02	−1.733	4.33𝐸−03
MAP2K5	Mitogen-activated protein kinase kinase 5	NM_002757 ///; NM_145160	Regulation of cell growth, protein amino acid phosphorylation, MAPKKK cascade, and signal transduction	−1.656	0.93𝐸−02	−1.504	1.90𝐸−02

Microarray analysis was performed at 3rd day of treatment on pooled RNAs from control cells and cells treated with 100 and 150 µg/mL of COLE from 2 independent experiments.