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Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production.

Zhang L, Zhou L, Du J, Li M, Qian C, Cheng Y, Peng Y, Xie J, Wang D - Biomed Res Int (2014)

Bottom Line: The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase.Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen.This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhi Road, Daping Yuzhong District, Chongqing 400042, China.

ABSTRACT
Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

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The ROS production of MM cells treated with ebselen in presence or absence of NAC was determined by Singlet ROS Probe. Fluorescence images of Singlet ROS Probe loaded cells were obtained under laser confocal microscopy ((A) DMSO, (B) ebselen 40 μM, and (C) ebselen 40 μM + NAC 15 mM). The average of fluorescence intensity obtained under FACS shows that ebselen induced ROS increasing of MM cells in a concentration (b) and time (c) manner. Each value represents the mean ± SD from three independent experiments. *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).
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fig3: The ROS production of MM cells treated with ebselen in presence or absence of NAC was determined by Singlet ROS Probe. Fluorescence images of Singlet ROS Probe loaded cells were obtained under laser confocal microscopy ((A) DMSO, (B) ebselen 40 μM, and (C) ebselen 40 μM + NAC 15 mM). The average of fluorescence intensity obtained under FACS shows that ebselen induced ROS increasing of MM cells in a concentration (b) and time (c) manner. Each value represents the mean ± SD from three independent experiments. *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).

Mentions: The preceding data indicated that ebselen is showed to be significantly toxic to MM cells. To determine whether the ebselen induced cytotoxic effects were mediated through oxidative stress, we measured the production of ROS in cell cultures challenged with ebselen in time and concentration manners. Then we found that, 4 h after treatment with different concentration ebselen, U266 and RPMI8226 cells demonstrated an increased level of ROS production (Figure 3(b)). After being treated with 40 μM ebselen for 2, 4, 8, and 24 hours, respectively, the production of ROS in cells increased markedly (Figure 3(c)).


Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production.

Zhang L, Zhou L, Du J, Li M, Qian C, Cheng Y, Peng Y, Xie J, Wang D - Biomed Res Int (2014)

The ROS production of MM cells treated with ebselen in presence or absence of NAC was determined by Singlet ROS Probe. Fluorescence images of Singlet ROS Probe loaded cells were obtained under laser confocal microscopy ((A) DMSO, (B) ebselen 40 μM, and (C) ebselen 40 μM + NAC 15 mM). The average of fluorescence intensity obtained under FACS shows that ebselen induced ROS increasing of MM cells in a concentration (b) and time (c) manner. Each value represents the mean ± SD from three independent experiments. *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921973&req=5

fig3: The ROS production of MM cells treated with ebselen in presence or absence of NAC was determined by Singlet ROS Probe. Fluorescence images of Singlet ROS Probe loaded cells were obtained under laser confocal microscopy ((A) DMSO, (B) ebselen 40 μM, and (C) ebselen 40 μM + NAC 15 mM). The average of fluorescence intensity obtained under FACS shows that ebselen induced ROS increasing of MM cells in a concentration (b) and time (c) manner. Each value represents the mean ± SD from three independent experiments. *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).
Mentions: The preceding data indicated that ebselen is showed to be significantly toxic to MM cells. To determine whether the ebselen induced cytotoxic effects were mediated through oxidative stress, we measured the production of ROS in cell cultures challenged with ebselen in time and concentration manners. Then we found that, 4 h after treatment with different concentration ebselen, U266 and RPMI8226 cells demonstrated an increased level of ROS production (Figure 3(b)). After being treated with 40 μM ebselen for 2, 4, 8, and 24 hours, respectively, the production of ROS in cells increased markedly (Figure 3(c)).

Bottom Line: The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase.Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen.This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhi Road, Daping Yuzhong District, Chongqing 400042, China.

ABSTRACT
Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

Show MeSH
Related in: MedlinePlus