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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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Related in: MedlinePlus

Ebselen induced apoptosis of MM cells analyzed by FACS, stained with annexin V-FITC/PI. (a) and (b) display the results of the cells treated with ebselen in a concentration and time dependent manner, respectively. The data is also showed in histogram (c). Data are presented as mean ± SD (n = 3). *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).
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fig2: Ebselen induced apoptosis of MM cells analyzed by FACS, stained with annexin V-FITC/PI. (a) and (b) display the results of the cells treated with ebselen in a concentration and time dependent manner, respectively. The data is also showed in histogram (c). Data are presented as mean ± SD (n = 3). *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).

Mentions: To test the effects of concentration and time of ebselen on apoptosis of MM cells, we measured apoptosis by flow cytometry using Annexin V-FITC/PI staining. It was found that ebselen was able to increase the percentages of apoptosis of cells in a concentration (Figure 2(a)) and time (Figure 2(b)) dependent manner (Figure 2(c)). When MM cells were treated with 10 μM ebselen for 24 hours, the apoptosis rate nearly doubled. The percentage of apoptotic cells was increased to 4 to 8 times when treated with 50 and 100 μM ebselen. In the time-course study, cells were treated with 40 μM ebselen for 6, 18, 24 hours, respectively, and then the data show that apoptosis rate was significantly increased with time.


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)

Ebselen induced apoptosis of MM cells analyzed by FACS, stained with annexin V-FITC/PI. (a) and (b) display the results of the cells treated with ebselen in a concentration and time dependent manner, respectively. The data is also showed in histogram (c). Data are presented as mean ± SD (n = 3). *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

fig2: Ebselen induced apoptosis of MM cells analyzed by FACS, stained with annexin V-FITC/PI. (a) and (b) display the results of the cells treated with ebselen in a concentration and time dependent manner, respectively. The data is also showed in histogram (c). Data are presented as mean ± SD (n = 3). *Significant difference compared to the control group (*P < 0.05, **P < 0.01, one-way ANOVA with Scheffe's test).
Mentions: To test the effects of concentration and time of ebselen on apoptosis of MM cells, we measured apoptosis by flow cytometry using Annexin V-FITC/PI staining. It was found that ebselen was able to increase the percentages of apoptosis of cells in a concentration (Figure 2(a)) and time (Figure 2(b)) dependent manner (Figure 2(c)). When MM cells were treated with 10 μM ebselen for 24 hours, the apoptosis rate nearly doubled. The percentage of apoptotic cells was increased to 4 to 8 times when treated with 50 and 100 μM ebselen. In the time-course study, cells were treated with 40 μM ebselen for 6, 18, 24 hours, respectively, and then the data show that apoptosis rate was significantly increased with time.

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