Genistein decreases cellular redox potential, partially suppresses cell growth in HL‑60 leukemia cells and sensitizes cells to γ‑radiation‑induced cell death

Kim,In  Gyu; Kim,Jin  Sik; Lee,Jae  Ha; Cho,Eun  Wie

doi:10.3892/mmr.2014.2611

Genistein decreases cellular redox potential, partially suppresses cell growth in HL‑60 leukemia cells and sensitizes cells to γ‑radiation‑induced cell death

Authors:
- In Gyu Kim
- Jin Sik Kim
- Jae Ha Lee
- Eun Wie Cho
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Affiliations: Department of Radiation Biology, Environment Radiation Research Group, Korea Atomic Energy Research Institute, Yuseong, Daejeon 305‑600, Republic of Korea, Bioconvergence Department, Korea Conformity Laboratories, Yoensu‑gu, Incheon 406‑840, Republic of Korea, Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong‑gu, Daejeon 305‑806, Republic of Korea
Published online on: October 8, 2014 https://doi.org/10.3892/mmr.2014.2611
Pages: 2786-2792
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Various mechanisms have been proposed to underlie the cellular activity of genistein, based on biological experiments and epidemiological studies. The present study demonstrated that genistein inhibited the expression of cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP)‑dependent isocitrate dehydrogenase (cICDH), thus increasing levels of intracellular reactive oxygen species (ROS) in human promyeloid leukemia HL‑60 cells. In genistein‑treated cells, the cellular redox potential (GSH/GSSG) was significantly decreased. This decrease in redox potential was caused by significant downregulation of the cICDH gene, generating the reducing equivalents (NADPH) for maintenance of cellular redox potential and cellular ROS level, which may regulate cell growth and cell death. Genistein‑induced ROS partially induced rapid transition into the G2/M phase by upregulation of p21wap1/cip1 and apoptotic cell death. Treatment of cells with N‑acetylcysteine, a well‑known antioxidant (ROS scavenger), not only partially restored cell growth and inhibited cell cycle arrest in G2/M, but also prevented apoptotic cell death. By contrast, normal lymphocytes did not significantly progress into the G2/M phase and radiation‑induced cell death was inhibited by genistein treatment. Therefore, genistein and γ‑irradiation together synergistically cause cell death in leukemia cells, however, genistein has a radioprotective effect in normal human lymphocytes. In conclusion, it was suggested that genistein selectively functions, not as an antioxidant, but as a pro‑oxidant in HL‑60 cells. This property can increase ionizing radiation‑induced cell cycle arrest and sensitivity to apoptotic cell death in human promyeloid leukemia HL‑60 cells, but does not cause significant damage to normal cells.

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