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

Kim IG, Kim JS, Lee JH, Cho EW - Mol Med Rep (2014)

Bottom Line: By contrast, normal lymphocytes did not significantly progress into the G2/M phase and radiation‑induced cell death was inhibited by genistein treatment.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Biology, Environment Radiation Research Group, Korea Atomic Energy Research Institute, Yuseong, Daejeon 305‑600, Republic of Korea.

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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Ge and γ-radiation-induced morphological alterations between human promyeloid leukemia HL-60 cells and normal human lymphocytes. Arrows indicate separated apoptotic cells (apoptotic bodies) Ge, Genistein.
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f5-mmr-10-06-2786: Ge and γ-radiation-induced morphological alterations between human promyeloid leukemia HL-60 cells and normal human lymphocytes. Arrows indicate separated apoptotic cells (apoptotic bodies) Ge, Genistein.

Mentions: Finally, it was confirmed that genistein had different effects on radiation-induced damage in promyeloid leukemia HL-60 cells and normal human lymphocytes by the detection of apoptotic bodies. At a dose of 2 Gy, a negligible number of γ-radiation-induced apoptotic bodies were detected in normal lymphocytes. However, radiation treatment partially induced initiation of apoptosis in HL-60 cells. Genistein clearly induced the formation of apoptotic bodies in certain HL-60 cells. However, it did not affect apoptotic body formation in normal lymphocytes. Genistein (20 μM) and γ-radiation synergistically increased apoptotic body formation in HL-60 cells. Furthermore, this combination treatment resulted in the formation of apoptotic bodies in HL-60 cells. However, significant numbers of apoptotic bodies were not observed in normal lymphocytes under any condition (Fig. 5).


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

Kim IG, Kim JS, Lee JH, Cho EW - Mol Med Rep (2014)

Ge and γ-radiation-induced morphological alterations between human promyeloid leukemia HL-60 cells and normal human lymphocytes. Arrows indicate separated apoptotic cells (apoptotic bodies) Ge, Genistein.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227428&req=5

f5-mmr-10-06-2786: Ge and γ-radiation-induced morphological alterations between human promyeloid leukemia HL-60 cells and normal human lymphocytes. Arrows indicate separated apoptotic cells (apoptotic bodies) Ge, Genistein.
Mentions: Finally, it was confirmed that genistein had different effects on radiation-induced damage in promyeloid leukemia HL-60 cells and normal human lymphocytes by the detection of apoptotic bodies. At a dose of 2 Gy, a negligible number of γ-radiation-induced apoptotic bodies were detected in normal lymphocytes. However, radiation treatment partially induced initiation of apoptosis in HL-60 cells. Genistein clearly induced the formation of apoptotic bodies in certain HL-60 cells. However, it did not affect apoptotic body formation in normal lymphocytes. Genistein (20 μM) and γ-radiation synergistically increased apoptotic body formation in HL-60 cells. Furthermore, this combination treatment resulted in the formation of apoptotic bodies in HL-60 cells. However, significant numbers of apoptotic bodies were not observed in normal lymphocytes under any condition (Fig. 5).

Bottom Line: By contrast, normal lymphocytes did not significantly progress into the G2/M phase and radiation‑induced cell death was inhibited by genistein treatment.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Biology, Environment Radiation Research Group, Korea Atomic Energy Research Institute, Yuseong, Daejeon 305‑600, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus