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

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

doi:10.3892/ijmm.2012.1115

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

Authors:
- Seunghee Bae
- Hye-Jung Jeong
- Hwa Jun Cha
- Karam Kim
- Yeong Min Choi
- In-Sook An
- Hyea Jung Koh
- Dae Jin Lim
- Su-Jae Lee
- Sungkwan An
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Affiliations: Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu, Seoul 143-701, Republic of Korea, Korea Institute for Skin and Clinical Sciences, Konkuk University, Gwangjin-gu, Seoul 143-701, Republic of Korea, Department of Beauty and Art, Suwon Women's College, Kyounggi-do 441-748, Republic of Korea, Graduate School of Arts, Hansung University, Seoul 136-792, Republic of Korea, Department of Chemistry, Hanyang University, Seongdong-gu, Seoul 133-791, Republic of Korea
Published online on: August 31, 2012 https://doi.org/10.3892/ijmm.2012.1115
Pages: 1180-1186

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Abstract

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.

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