Apoptosis of Human Leukemia HL-60 Cells and Murine Leukemia WEHI-3 Cells Induced by Berberine through the Activation of Caspase-3
The aim of this study was to clarify the mechanisms of apoptosis, cytotoxicity, DNA damage and fragmentation, as well as the production of reactive oxygen species (ROS) and Ca +2 , induced by berberine in human promyelocytic leukemia HL-60 and murine myelomonocytic leukemia WEHI-3 cells. The levels...
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Published in | Anticancer research Vol. 26; no. 1A; pp. 227 - 242 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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International Institute of Anticancer Research
01.01.2006
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Abstract | The aim of this study was to clarify the mechanisms of apoptosis, cytotoxicity, DNA damage and fragmentation, as well as the
production of reactive oxygen species (ROS) and Ca +2 , induced by berberine in human promyelocytic leukemia HL-60 and murine myelomonocytic leukemia WEHI-3 cells. The levels of
Bcl-2 and Bax, the changes of mitochondria membrane potential (MMP), cytochrome c release and activation of caspase-3 were
also investigated in both cell lines. The flow cytometry and DAPI staining assays indicated that berberine induced cytotoxicity
in both cell lines examined. Flow cytometry assay also showed that berberine induced ROS and Ca +2 production, decreased the levels of MMP and increased the activity of caspase-3 in both cell lines examined. Berberine-induced
apoptosis was accompanied by increased levels of Ca +2 and a decrease in the mitochondrial membrane potential, leading to the release of cytochrome c and the cleavage of pro-caspase-3.
Western blotting also showed that berberine increased the levels of Bax and cytochrome c and decreased the levels of Bcl-2
in both cell lines. Inhibition of caspase-3 activation (z-VAD-fmk: cell-permeable broad-spectrum caspase inhibitor) completely
blocked berberine-induced apoptosis in both HL-60 and WEHI-3 cells. Therefore, berberine induced apoptosis in both examined
cell lines through the activation of caspase-3. |
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AbstractList | The aim of this study was to clarify the mechanisms of apoptosis, cytotoxicity, DNA damage and fragmentation, as well as the
production of reactive oxygen species (ROS) and Ca +2 , induced by berberine in human promyelocytic leukemia HL-60 and murine myelomonocytic leukemia WEHI-3 cells. The levels of
Bcl-2 and Bax, the changes of mitochondria membrane potential (MMP), cytochrome c release and activation of caspase-3 were
also investigated in both cell lines. The flow cytometry and DAPI staining assays indicated that berberine induced cytotoxicity
in both cell lines examined. Flow cytometry assay also showed that berberine induced ROS and Ca +2 production, decreased the levels of MMP and increased the activity of caspase-3 in both cell lines examined. Berberine-induced
apoptosis was accompanied by increased levels of Ca +2 and a decrease in the mitochondrial membrane potential, leading to the release of cytochrome c and the cleavage of pro-caspase-3.
Western blotting also showed that berberine increased the levels of Bax and cytochrome c and decreased the levels of Bcl-2
in both cell lines. Inhibition of caspase-3 activation (z-VAD-fmk: cell-permeable broad-spectrum caspase inhibitor) completely
blocked berberine-induced apoptosis in both HL-60 and WEHI-3 cells. Therefore, berberine induced apoptosis in both examined
cell lines through the activation of caspase-3. The aim of this study was to clarify the mechanisms of apoptosis, cytotoxicity, DNA damage and fragmentation, as well as the production of reactive oxygen species (ROS) and Ca+2, induced by berberine in human promyelocytic leukemia HL-60 and murine myelomonocytic leukemia WEHI-3 cells. The levels of Bcl-2 and Bax, the changes of mitochondria membrane potential (MMP), cytochrome c release and activation of caspase-3 were also investigated in both cell lines. The flow cytometry and DAPI staining assays indicated that berberine induced cytotoxicity in both cell lines examined. Flow cytometry assay also showed that berberine induced ROS and Ca+2 production, decreased the levels of MMP and increased the activity of caspase-3 in both cell lines examined. Berberine-induced apoptosis was accompanied by increased levels of Ca+2 and a decrease in the mitochondrial membrane potential, leading to the release of cytochrome c and the cleavage of pro-caspase-3. Western blotting also showed that berberine increased the levels of Bax and cytochrome c and decreased the levels of Bcl-2 in both cell lines. Inhibition of caspase-3 activation (z-VAD-fmk: cell-permeable broad-spectrum caspase inhibitor) completely blocked berberine-induced apoptosis in both HL-60 and WEHI-3 cells. Therefore, berberine induced apoptosis in both examined cell lines through the activation of caspase-3. |
Author | HENG-CHIEN HO SHUNG-TE KAO CHIN-CHUNG LIN GUANG-WEI CHEN JING-GUNG CHUNG |
Author_xml | – sequence: 1 givenname: Chin-Chung surname: LIN fullname: LIN, Chin-Chung organization: Graduate Institute of Chinese Medical Science, School of Chinese Medicine, China Medical University, 91, Hsueh-Shih Road, Taichung City 404, Taiwan, Province of China – sequence: 2 givenname: Shung-Te surname: KAO fullname: KAO, Shung-Te organization: Graduate Institute of Chinese Medical Science, School of Chinese Medicine, China Medical University, 91, Hsueh-Shih Road, Taichung City 404, Taiwan, Province of China – sequence: 3 givenname: Guang-Wei surname: CHEN fullname: CHEN, Guang-Wei organization: Graduate Institute of Chinese Medical Science, School of Chinese Medicine, China Medical University, 91, Hsueh-Shih Road, Taichung City 404, Taiwan, Province of China – sequence: 4 givenname: Heng-Chien surname: HO fullname: HO, Heng-Chien organization: Cancer Research Center, Department of Medical Research, China Medical University Hospital, Taichung City 404, Taiwan, Province of China – sequence: 5 givenname: Jing-Gung surname: CHUNG fullname: CHUNG, Jing-Gung organization: Department of Microbiology, China Medical University, 91, Hsueh-Shih Road, Taichung City 404, Taiwan, Province of China |
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Keywords | Human Berberine mitochondria membrane potential Enzyme Cysteine endopeptidases Leukemia Rodentia Electrophysiology Malignant hemopathy HL60 cell line Peptidases Alkaloid Vertebrata Mitochondria Mammalia Cancerology Mouse Cell death Animal Hydrolases Membrane potential leukemia cells Apoptosis caspase-3 |
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Snippet | The aim of this study was to clarify the mechanisms of apoptosis, cytotoxicity, DNA damage and fragmentation, as well as the
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SubjectTerms | Animals Apoptosis - drug effects bcl-2-Associated X Protein - metabolism bcl-Associated Death Protein - metabolism Berberine - pharmacology Biological and medical sciences Blotting, Western Calcium - metabolism Caspase 3 Caspase Inhibitors Caspases - metabolism Cell Survival - drug effects Cytochromes c - metabolism Enzyme Activation - drug effects Fluorescent Dyes - chemistry Hematologic and hematopoietic diseases HL-60 Cells Humans Indoles - chemistry Intracellular Membranes - drug effects Intracellular Membranes - physiology Leukemia, Myeloid - drug therapy Leukemia, Myeloid - metabolism Leukemia, Myeloid - pathology Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - metabolism Leukemia, Promyelocytic, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Membrane Potentials - drug effects Membrane Potentials - physiology Mice Mitochondria - drug effects Mitochondria - physiology Proto-Oncogene Proteins c-bcl-2 - biosynthesis Proto-Oncogene Proteins c-bcl-2 - metabolism Reactive Oxygen Species - metabolism Tumors |
Title | Apoptosis of Human Leukemia HL-60 Cells and Murine Leukemia WEHI-3 Cells Induced by Berberine through the Activation of Caspase-3 |
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