ACTIVATION OF AMP-ACTIVATED PROTEIN KINASE AMELIORATES CYTARABINE-INDUCED OVEREXPRESSION OF NUCLEOPHOSMIN AND DRUG-INDUCED-CHEMORESISTANCE IN HL-60 AML CELLS
(Abstract release date: 05/19/16)
EHA Library. Kim D. 06/09/16; 134546; PB1646
Prof. Dr. Dana Kim
Contributions
Contributions
Abstract
Abstract: PB1646
Type: Publication Only
Background
Nucleophosmin (NPM or B23) is a ribosomal protein located mainly in nucleolus, and multifunctional enzyme in cancer cell growth and protein synthesis. Particularly, it has been suggested that NPM plays a role in the positive regulation of cell proliferation, thus observed the over-expression levels in pathological higher grades of tumor and actively proliferating cells than normal cells. On the other hand, AMP-activated protein kinase (AMPK) is a critical energy sensor to regulate homeostasis and plays a potential role for anti-cell proliferating activity.
Aims
We investigated the effects of AMPK activation on the cell death (apoptosis) and NPM expression in AML (acute myeloid leukemia) cells (HL-60) treated with low or high dose of an antileukemic drug cytarabine to understand the mechanisms responsible for AML cells chemoresistance.
Methods
Cell viability was assessed using MTS assay. Apoptosis and cell cycle progression were evaluated by flow cytometry assay. Protein and mRNA expressions were detected with real time-PCR and Western blot assay.
Results
Interestingly, we found that the level of NPM expression was increased significantly in cytarabine-treated cells without dose-dependency of cell death, indicating the drug-induced cell resistance. In the same point, cytarabine also inhibited the phosphor-activity (Thr172) and expression level of AMPK, which has mTOR-p70S6K pathway-repressor activity. As expected, single cytarabine treatment increased the ratio of p-mTOR/mTOR and p-p70S6K/p70S6K. Co-treatment of AMPK activator (phenformin or AICAR) in cytarabine-treated HL-60 AML cells inhibited significantly the induction of NPM expression level with the decrease of phosphor-activities of mTOR and its substrate p70S6K, resulted in the accelerated cell apoptosis.
Conclusion
Our results suggest that AMPK activation might be used to sensitize AML cells to cytarabine with the control of NPM expression levels, thus the lower therapeutic dose and the less adverse effects.(Correspondence to HG Yi and CS Park; Medical Research Center no. 2014009392)
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
Type: Publication Only
Background
Nucleophosmin (NPM or B23) is a ribosomal protein located mainly in nucleolus, and multifunctional enzyme in cancer cell growth and protein synthesis. Particularly, it has been suggested that NPM plays a role in the positive regulation of cell proliferation, thus observed the over-expression levels in pathological higher grades of tumor and actively proliferating cells than normal cells. On the other hand, AMP-activated protein kinase (AMPK) is a critical energy sensor to regulate homeostasis and plays a potential role for anti-cell proliferating activity.
Aims
We investigated the effects of AMPK activation on the cell death (apoptosis) and NPM expression in AML (acute myeloid leukemia) cells (HL-60) treated with low or high dose of an antileukemic drug cytarabine to understand the mechanisms responsible for AML cells chemoresistance.
Methods
Cell viability was assessed using MTS assay. Apoptosis and cell cycle progression were evaluated by flow cytometry assay. Protein and mRNA expressions were detected with real time-PCR and Western blot assay.
Results
Interestingly, we found that the level of NPM expression was increased significantly in cytarabine-treated cells without dose-dependency of cell death, indicating the drug-induced cell resistance. In the same point, cytarabine also inhibited the phosphor-activity (Thr172) and expression level of AMPK, which has mTOR-p70S6K pathway-repressor activity. As expected, single cytarabine treatment increased the ratio of p-mTOR/mTOR and p-p70S6K/p70S6K. Co-treatment of AMPK activator (phenformin or AICAR) in cytarabine-treated HL-60 AML cells inhibited significantly the induction of NPM expression level with the decrease of phosphor-activities of mTOR and its substrate p70S6K, resulted in the accelerated cell apoptosis.
Conclusion
Our results suggest that AMPK activation might be used to sensitize AML cells to cytarabine with the control of NPM expression levels, thus the lower therapeutic dose and the less adverse effects.(Correspondence to HG Yi and CS Park; Medical Research Center no. 2014009392)
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
Abstract: PB1646
Type: Publication Only
Background
Nucleophosmin (NPM or B23) is a ribosomal protein located mainly in nucleolus, and multifunctional enzyme in cancer cell growth and protein synthesis. Particularly, it has been suggested that NPM plays a role in the positive regulation of cell proliferation, thus observed the over-expression levels in pathological higher grades of tumor and actively proliferating cells than normal cells. On the other hand, AMP-activated protein kinase (AMPK) is a critical energy sensor to regulate homeostasis and plays a potential role for anti-cell proliferating activity.
Aims
We investigated the effects of AMPK activation on the cell death (apoptosis) and NPM expression in AML (acute myeloid leukemia) cells (HL-60) treated with low or high dose of an antileukemic drug cytarabine to understand the mechanisms responsible for AML cells chemoresistance.
Methods
Cell viability was assessed using MTS assay. Apoptosis and cell cycle progression were evaluated by flow cytometry assay. Protein and mRNA expressions were detected with real time-PCR and Western blot assay.
Results
Interestingly, we found that the level of NPM expression was increased significantly in cytarabine-treated cells without dose-dependency of cell death, indicating the drug-induced cell resistance. In the same point, cytarabine also inhibited the phosphor-activity (Thr172) and expression level of AMPK, which has mTOR-p70S6K pathway-repressor activity. As expected, single cytarabine treatment increased the ratio of p-mTOR/mTOR and p-p70S6K/p70S6K. Co-treatment of AMPK activator (phenformin or AICAR) in cytarabine-treated HL-60 AML cells inhibited significantly the induction of NPM expression level with the decrease of phosphor-activities of mTOR and its substrate p70S6K, resulted in the accelerated cell apoptosis.
Conclusion
Our results suggest that AMPK activation might be used to sensitize AML cells to cytarabine with the control of NPM expression levels, thus the lower therapeutic dose and the less adverse effects.(Correspondence to HG Yi and CS Park; Medical Research Center no. 2014009392)
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
Type: Publication Only
Background
Nucleophosmin (NPM or B23) is a ribosomal protein located mainly in nucleolus, and multifunctional enzyme in cancer cell growth and protein synthesis. Particularly, it has been suggested that NPM plays a role in the positive regulation of cell proliferation, thus observed the over-expression levels in pathological higher grades of tumor and actively proliferating cells than normal cells. On the other hand, AMP-activated protein kinase (AMPK) is a critical energy sensor to regulate homeostasis and plays a potential role for anti-cell proliferating activity.
Aims
We investigated the effects of AMPK activation on the cell death (apoptosis) and NPM expression in AML (acute myeloid leukemia) cells (HL-60) treated with low or high dose of an antileukemic drug cytarabine to understand the mechanisms responsible for AML cells chemoresistance.
Methods
Cell viability was assessed using MTS assay. Apoptosis and cell cycle progression were evaluated by flow cytometry assay. Protein and mRNA expressions were detected with real time-PCR and Western blot assay.
Results
Interestingly, we found that the level of NPM expression was increased significantly in cytarabine-treated cells without dose-dependency of cell death, indicating the drug-induced cell resistance. In the same point, cytarabine also inhibited the phosphor-activity (Thr172) and expression level of AMPK, which has mTOR-p70S6K pathway-repressor activity. As expected, single cytarabine treatment increased the ratio of p-mTOR/mTOR and p-p70S6K/p70S6K. Co-treatment of AMPK activator (phenformin or AICAR) in cytarabine-treated HL-60 AML cells inhibited significantly the induction of NPM expression level with the decrease of phosphor-activities of mTOR and its substrate p70S6K, resulted in the accelerated cell apoptosis.
Conclusion
Our results suggest that AMPK activation might be used to sensitize AML cells to cytarabine with the control of NPM expression levels, thus the lower therapeutic dose and the less adverse effects.(Correspondence to HG Yi and CS Park; Medical Research Center no. 2014009392)
Session topic: E-poster
Keyword(s): Acute myeloid leukemia
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