A GENOME-WIDE ANALYSES OF DIFFERENTIALLY EXPRESSED GENES AND RELATED NETWORKS AFFECTED BY FISETIN AND HESPERETIN IN CHRONIC MYELOID LEUKEMIA CELLS
(Abstract release date: 05/21/15)
EHA Library. Adan Gökbulut A. 06/12/15; 102607; PB1734
Disclosure(s): ?zmir Institute of TechnologyMolecular Biology and Genetics
Dr. Aysun Adan Gökbulut
Contributions
Contributions
Abstract
Abstract: PB1734
Type: Publication Only
Background
Diet is an important determinant of cancer risk based on various epidemiologic and case control studies. Therefore, there is a great interest to investigate bioactive food components for their cancer preventive and therapeutic potentials. Fisetin and hesperetin are members of the flavonoid polyphenols, found in several plant species. They have a wide range of pharmacological properties including antioxidant, anti-inflammatory and anticancer effects. Their chemopreventive/chemotherapeutic potentials were investigated in several cancer types such as colon and prostate cancers, however, the exact mechanisms of fisetin and hesperetin actions are not known in CML.
Aims
We aimed at determining the underlying molecular mechanisms of fisetin and hesperetin induced growth inhibitory effects in K562 CML cells based on changes in global gene expression patterns using genome-wide microarray analysis.
Methods
Expression profiling is accomplished using the Human HT-12v4 beadchip microarrays (Illumina, Inc.). Total RNA isolated from fisetin and hesperetin treated K562 CML cells was converted to biotin labeled cRNA, which were hybridized to beadchips. The BeadChips were analyzed using Illumina’s Genome Studio in order to cluster genes. We obtained the list of differentially expressed genes based on p-value <0.05 and at least 2.0 fold change. Affected genetic networks were determined by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Analysis (IPA).
Results
A total of 553 and 1734 genes were significantl regulated (P<0.05) in 50 μM and 100 μM fisetin treated K562 cells, respectively. Both 50 and 100 μM fisetin treatment resulted in the upregulation of common genes such as NFKBIA, NOXA, p21 and GADD45B. We also found each fisetin concentration altered expression of specific genes. For instance, 50 μM fisetin upregulated NFKBIZ and GADD45A while 100 μM fisetin treatment resulted in the upregulation of CDKN2D/ p19, TXNIP and SMAD5. Furthermore, MYC, MYB, C-KIT, TUBA1A and TUBAL3 were some of common downregulated genes after 50 and 100 μM fisetin treatment. 100 μM fisetin also caused downregulation of important genes such as FOXK1, FOXA2 and BCL-XL. Apoptosis modulation, TP53 network, TNF-α, KIT receptor and JAK/STAT signaling, adhesion networks, growth hormone receptor signaling and angiogenesis were modulated networks. On the other hand, a total of 1659 and 1201 genes were significantly changed (P<0.05) in 100 and 150 μM hesperetin treated K562 cells, respectively. DUSP1, CDKN1A, GADD45B and BIM were the examples of common upregulated genes in 100 and 150 μM hesperetin treatment. On the other hand, 100 μM hesperetin also upregulated some other genes such as p27, CASP4, DUSP5 whereas 150 μM hesperetin upregulated MT1A, DUSP3 and NFKBIA. STAT5A, TUBA1A, MYB, KIT, EPCAM and PCNA were the examples of common downregulated genes in 100 and 150 μM hesperetin treatment. 100 μM hesperetin treatment also resulted in the downregulation of EEF1G, POLR2B and STAT3. Furthermore, 150 μM hesperetin treatment downregulated genes such as MCM10, ABCC4 and POLE2. Translation initiation and elongation networks, replication and trancription networks, EGF, JAK/STAT and KIT receptor signaling pathways, growth hormon receptor signaling and PI3K pathway were altered networks.
Summary
Keyword(s): C-kit, Chronic myeloid leukemia, Gene expression profile, Microarray analysis
Type: Publication Only
Background
Diet is an important determinant of cancer risk based on various epidemiologic and case control studies. Therefore, there is a great interest to investigate bioactive food components for their cancer preventive and therapeutic potentials. Fisetin and hesperetin are members of the flavonoid polyphenols, found in several plant species. They have a wide range of pharmacological properties including antioxidant, anti-inflammatory and anticancer effects. Their chemopreventive/chemotherapeutic potentials were investigated in several cancer types such as colon and prostate cancers, however, the exact mechanisms of fisetin and hesperetin actions are not known in CML.
Aims
We aimed at determining the underlying molecular mechanisms of fisetin and hesperetin induced growth inhibitory effects in K562 CML cells based on changes in global gene expression patterns using genome-wide microarray analysis.
Methods
Expression profiling is accomplished using the Human HT-12v4 beadchip microarrays (Illumina, Inc.). Total RNA isolated from fisetin and hesperetin treated K562 CML cells was converted to biotin labeled cRNA, which were hybridized to beadchips. The BeadChips were analyzed using Illumina’s Genome Studio in order to cluster genes. We obtained the list of differentially expressed genes based on p-value <0.05 and at least 2.0 fold change. Affected genetic networks were determined by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Analysis (IPA).
Results
A total of 553 and 1734 genes were significantl regulated (P<0.05) in 50 μM and 100 μM fisetin treated K562 cells, respectively. Both 50 and 100 μM fisetin treatment resulted in the upregulation of common genes such as NFKBIA, NOXA, p21 and GADD45B. We also found each fisetin concentration altered expression of specific genes. For instance, 50 μM fisetin upregulated NFKBIZ and GADD45A while 100 μM fisetin treatment resulted in the upregulation of CDKN2D/ p19, TXNIP and SMAD5. Furthermore, MYC, MYB, C-KIT, TUBA1A and TUBAL3 were some of common downregulated genes after 50 and 100 μM fisetin treatment. 100 μM fisetin also caused downregulation of important genes such as FOXK1, FOXA2 and BCL-XL. Apoptosis modulation, TP53 network, TNF-α, KIT receptor and JAK/STAT signaling, adhesion networks, growth hormone receptor signaling and angiogenesis were modulated networks. On the other hand, a total of 1659 and 1201 genes were significantly changed (P<0.05) in 100 and 150 μM hesperetin treated K562 cells, respectively. DUSP1, CDKN1A, GADD45B and BIM were the examples of common upregulated genes in 100 and 150 μM hesperetin treatment. On the other hand, 100 μM hesperetin also upregulated some other genes such as p27, CASP4, DUSP5 whereas 150 μM hesperetin upregulated MT1A, DUSP3 and NFKBIA. STAT5A, TUBA1A, MYB, KIT, EPCAM and PCNA were the examples of common downregulated genes in 100 and 150 μM hesperetin treatment. 100 μM hesperetin treatment also resulted in the downregulation of EEF1G, POLR2B and STAT3. Furthermore, 150 μM hesperetin treatment downregulated genes such as MCM10, ABCC4 and POLE2. Translation initiation and elongation networks, replication and trancription networks, EGF, JAK/STAT and KIT receptor signaling pathways, growth hormon receptor signaling and PI3K pathway were altered networks.
Summary
Fisetin and hesperetin trigger apoptosis and growth suppression via affecting various significant targets in K562 cells, which could open the usage of new strategies together with fisetin to overcome difficulties in CML treatment.
Keyword(s): C-kit, Chronic myeloid leukemia, Gene expression profile, Microarray analysis
Abstract: PB1734
Type: Publication Only
Background
Diet is an important determinant of cancer risk based on various epidemiologic and case control studies. Therefore, there is a great interest to investigate bioactive food components for their cancer preventive and therapeutic potentials. Fisetin and hesperetin are members of the flavonoid polyphenols, found in several plant species. They have a wide range of pharmacological properties including antioxidant, anti-inflammatory and anticancer effects. Their chemopreventive/chemotherapeutic potentials were investigated in several cancer types such as colon and prostate cancers, however, the exact mechanisms of fisetin and hesperetin actions are not known in CML.
Aims
We aimed at determining the underlying molecular mechanisms of fisetin and hesperetin induced growth inhibitory effects in K562 CML cells based on changes in global gene expression patterns using genome-wide microarray analysis.
Methods
Expression profiling is accomplished using the Human HT-12v4 beadchip microarrays (Illumina, Inc.). Total RNA isolated from fisetin and hesperetin treated K562 CML cells was converted to biotin labeled cRNA, which were hybridized to beadchips. The BeadChips were analyzed using Illumina’s Genome Studio in order to cluster genes. We obtained the list of differentially expressed genes based on p-value <0.05 and at least 2.0 fold change. Affected genetic networks were determined by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Analysis (IPA).
Results
A total of 553 and 1734 genes were significantl regulated (P<0.05) in 50 μM and 100 μM fisetin treated K562 cells, respectively. Both 50 and 100 μM fisetin treatment resulted in the upregulation of common genes such as NFKBIA, NOXA, p21 and GADD45B. We also found each fisetin concentration altered expression of specific genes. For instance, 50 μM fisetin upregulated NFKBIZ and GADD45A while 100 μM fisetin treatment resulted in the upregulation of CDKN2D/ p19, TXNIP and SMAD5. Furthermore, MYC, MYB, C-KIT, TUBA1A and TUBAL3 were some of common downregulated genes after 50 and 100 μM fisetin treatment. 100 μM fisetin also caused downregulation of important genes such as FOXK1, FOXA2 and BCL-XL. Apoptosis modulation, TP53 network, TNF-α, KIT receptor and JAK/STAT signaling, adhesion networks, growth hormone receptor signaling and angiogenesis were modulated networks. On the other hand, a total of 1659 and 1201 genes were significantly changed (P<0.05) in 100 and 150 μM hesperetin treated K562 cells, respectively. DUSP1, CDKN1A, GADD45B and BIM were the examples of common upregulated genes in 100 and 150 μM hesperetin treatment. On the other hand, 100 μM hesperetin also upregulated some other genes such as p27, CASP4, DUSP5 whereas 150 μM hesperetin upregulated MT1A, DUSP3 and NFKBIA. STAT5A, TUBA1A, MYB, KIT, EPCAM and PCNA were the examples of common downregulated genes in 100 and 150 μM hesperetin treatment. 100 μM hesperetin treatment also resulted in the downregulation of EEF1G, POLR2B and STAT3. Furthermore, 150 μM hesperetin treatment downregulated genes such as MCM10, ABCC4 and POLE2. Translation initiation and elongation networks, replication and trancription networks, EGF, JAK/STAT and KIT receptor signaling pathways, growth hormon receptor signaling and PI3K pathway were altered networks.
Summary
Keyword(s): C-kit, Chronic myeloid leukemia, Gene expression profile, Microarray analysis
Type: Publication Only
Background
Diet is an important determinant of cancer risk based on various epidemiologic and case control studies. Therefore, there is a great interest to investigate bioactive food components for their cancer preventive and therapeutic potentials. Fisetin and hesperetin are members of the flavonoid polyphenols, found in several plant species. They have a wide range of pharmacological properties including antioxidant, anti-inflammatory and anticancer effects. Their chemopreventive/chemotherapeutic potentials were investigated in several cancer types such as colon and prostate cancers, however, the exact mechanisms of fisetin and hesperetin actions are not known in CML.
Aims
We aimed at determining the underlying molecular mechanisms of fisetin and hesperetin induced growth inhibitory effects in K562 CML cells based on changes in global gene expression patterns using genome-wide microarray analysis.
Methods
Expression profiling is accomplished using the Human HT-12v4 beadchip microarrays (Illumina, Inc.). Total RNA isolated from fisetin and hesperetin treated K562 CML cells was converted to biotin labeled cRNA, which were hybridized to beadchips. The BeadChips were analyzed using Illumina’s Genome Studio in order to cluster genes. We obtained the list of differentially expressed genes based on p-value <0.05 and at least 2.0 fold change. Affected genetic networks were determined by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Analysis (IPA).
Results
A total of 553 and 1734 genes were significantl regulated (P<0.05) in 50 μM and 100 μM fisetin treated K562 cells, respectively. Both 50 and 100 μM fisetin treatment resulted in the upregulation of common genes such as NFKBIA, NOXA, p21 and GADD45B. We also found each fisetin concentration altered expression of specific genes. For instance, 50 μM fisetin upregulated NFKBIZ and GADD45A while 100 μM fisetin treatment resulted in the upregulation of CDKN2D/ p19, TXNIP and SMAD5. Furthermore, MYC, MYB, C-KIT, TUBA1A and TUBAL3 were some of common downregulated genes after 50 and 100 μM fisetin treatment. 100 μM fisetin also caused downregulation of important genes such as FOXK1, FOXA2 and BCL-XL. Apoptosis modulation, TP53 network, TNF-α, KIT receptor and JAK/STAT signaling, adhesion networks, growth hormone receptor signaling and angiogenesis were modulated networks. On the other hand, a total of 1659 and 1201 genes were significantly changed (P<0.05) in 100 and 150 μM hesperetin treated K562 cells, respectively. DUSP1, CDKN1A, GADD45B and BIM were the examples of common upregulated genes in 100 and 150 μM hesperetin treatment. On the other hand, 100 μM hesperetin also upregulated some other genes such as p27, CASP4, DUSP5 whereas 150 μM hesperetin upregulated MT1A, DUSP3 and NFKBIA. STAT5A, TUBA1A, MYB, KIT, EPCAM and PCNA were the examples of common downregulated genes in 100 and 150 μM hesperetin treatment. 100 μM hesperetin treatment also resulted in the downregulation of EEF1G, POLR2B and STAT3. Furthermore, 150 μM hesperetin treatment downregulated genes such as MCM10, ABCC4 and POLE2. Translation initiation and elongation networks, replication and trancription networks, EGF, JAK/STAT and KIT receptor signaling pathways, growth hormon receptor signaling and PI3K pathway were altered networks.
Summary
Fisetin and hesperetin trigger apoptosis and growth suppression via affecting various significant targets in K562 cells, which could open the usage of new strategies together with fisetin to overcome difficulties in CML treatment.
Keyword(s): C-kit, Chronic myeloid leukemia, Gene expression profile, Microarray analysis
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