The hypoxia-mimetic agent cobalt chloride induces cell cycle arrest and alters gene expression in U266 multiple myeloma cells

Hypoxia is a common feature of tumors that occurs across a wide variety of malignancies. Multiple myeloma is an incurable malignant disorder of plasma cells in the bone marrow. Although bone marrow hypoxia is crucial for normal hematopoiesis, the effect of hypoxia on multiple myeloma is poorly under...

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Bibliographic Details
Published in:International journal of molecular medicine 2012-11, Vol.30 (5), p.1180-1186
Main Authors: BAE, SEUNGHEE, JEONG, HYE-JUNG, CHA, HWA JUN, KIM, KARAM, CHOI, YEONG MIN, AN, IN-SOOK, KOH, HYEA JUNG, LIM, DAE JIN, LEE, SU-JAE, AN, SUNGKWAN
Format: Article
Language:English
Subjects:
Angiogenesis
Apoptosis
Cancer
Cell cycle
cell cycle arrest
Cell growth
cobalt chloride
Gene expression
Hypoxia
Kinases
Metastasis
Multiple myeloma
Proteins
Rodents
Statistical analysis
Vascular endothelial growth factor
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Summary:Hypoxia is a common feature of tumors that occurs across a wide variety of malignancies. Multiple myeloma is an incurable malignant disorder of plasma cells in the bone marrow. Although bone marrow hypoxia is crucial for normal hematopoiesis, the effect of hypoxia on multiple myeloma is poorly understood. In this study, we demonstrated that cobalt chloride (CoCl2)-mediated hypoxia decreased cell viability and altered gene expression in U266 human multiple myeloma cells. CoCl2 induced the loss of cell viability in a concentration-dependent manner. In addition, FACS analysis revealed that the loss of cell viability was related to apoptosis. Using microarray analysis, we identified mRNA expression profile changes in response to CoCl2 treatment in U266 cells. Four hundred and fifty-two mRNAs exhibited >2-fold changes in expression in CoCl2-treated U266 cells compared to their expression in control cells. A follow-up bioinformatics study revealed that a great number of genes with altered expression were involved in apoptosis, cell cycle, transcription and development. In conclusion, these results provide novel evidence that CoCl2-mediated hypoxia affects the expression profiles of genes that are functionally related to apoptosis and angiogenesis in U266 multiple myeloma cells.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2012.1115