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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 mitochondrial cytochrome C release from the mitochondria to cytosol. A representative immunoblot of MM cell cultures in presence or absence of ebselen showing levels of cytochrome C in cytosolic and mitochondrial extracts. Cells were treated for 4 h with ebselen. COX-IV and β-actin protein levels were used as internal reference of mitochondrial and cytosol, respectively. The record shown is representative of three experiments.
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fig6: Ebselen induced mitochondrial cytochrome C release from the mitochondria to cytosol. A representative immunoblot of MM cell cultures in presence or absence of ebselen showing levels of cytochrome C in cytosolic and mitochondrial extracts. Cells were treated for 4 h with ebselen. COX-IV and β-actin protein levels were used as internal reference of mitochondrial and cytosol, respectively. The record shown is representative of three experiments.

Mentions: Mitochondrial cytochrome C release to the cytosol is considered to be one of the key steps in cell death pathways. In order to ascertain if this occurred in our study, levels of cytochrome C were determined by Western blot in cytosolic fractions and mitochondrial fractions, respectively, from cell culture treated with 40 μM ebselen for 4 hours. The result shows that cell cultures challenged with 40 μM ebselen for 4 hours were accompanied with cytochrome C release from the mitochondria to cytosol (Figure 6).


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 mitochondrial cytochrome C release from the mitochondria to cytosol. A representative immunoblot of MM cell cultures in presence or absence of ebselen showing levels of cytochrome C in cytosolic and mitochondrial extracts. Cells were treated for 4 h with ebselen. COX-IV and β-actin protein levels were used as internal reference of mitochondrial and cytosol, respectively. The record shown is representative of three experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Ebselen induced mitochondrial cytochrome C release from the mitochondria to cytosol. A representative immunoblot of MM cell cultures in presence or absence of ebselen showing levels of cytochrome C in cytosolic and mitochondrial extracts. Cells were treated for 4 h with ebselen. COX-IV and β-actin protein levels were used as internal reference of mitochondrial and cytosol, respectively. The record shown is representative of three experiments.
Mentions: Mitochondrial cytochrome C release to the cytosol is considered to be one of the key steps in cell death pathways. In order to ascertain if this occurred in our study, levels of cytochrome C were determined by Western blot in cytosolic fractions and mitochondrial fractions, respectively, from cell culture treated with 40 μM ebselen for 4 hours. The result shows that cell cultures challenged with 40 μM ebselen for 4 hours were accompanied with cytochrome C release from the mitochondria to cytosol (Figure 6).

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