Limits...
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.

Show MeSH

Related in: MedlinePlus

Bax translocation to mitochondria from cytoplasm after being treated with ebselen is determined by Western blot. (a) Ebselen decrased Bax level in cytoplasm in a concentration and time dependent manner. (b) Mitochondria Bax level increased and cytoplasmic Bax level decreased in MM cells treated with ebselen 40 μM for 4 hours. (c) The decreasing of cytoplasmic Bax level can be recovered partially by 15 mM NAC.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921973&req=5

fig4: Bax translocation to mitochondria from cytoplasm after being treated with ebselen is determined by Western blot. (a) Ebselen decrased Bax level in cytoplasm in a concentration and time dependent manner. (b) Mitochondria Bax level increased and cytoplasmic Bax level decreased in MM cells treated with ebselen 40 μM for 4 hours. (c) The decreasing of cytoplasmic Bax level can be recovered partially by 15 mM NAC.

Mentions: Bax belongs to Bcl-2 family which is involved in apoptosis; there are some works which reported that Bax can be translocated to mitochondria after a cytotoxic stimulus [22]. So the next set of experiments were designed to find out if the Bax protein in MM cells behaved as others described after being treated with ebselen. Then we measured Bax by Western blot, including its expression and location. The result indicated that the Bax levels in the cytosol fraction were decreased after ebselen treatment in a concentration and time dependent manner (Figure 4(a)). After 40 μM ebselen treatment of MM cells for 4 hours, the Bax levels increased significantly in mitochondrial fraction and, in contrast, decreased in cytosol fraction (Figure 4(b)), which mean that ebselen can induce Bax translocation to mitochondria from cytosol.


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)

Bax translocation to mitochondria from cytoplasm after being treated with ebselen is determined by Western blot. (a) Ebselen decrased Bax level in cytoplasm in a concentration and time dependent manner. (b) Mitochondria Bax level increased and cytoplasmic Bax level decreased in MM cells treated with ebselen 40 μM for 4 hours. (c) The decreasing of cytoplasmic Bax level can be recovered partially by 15 mM NAC.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Bax translocation to mitochondria from cytoplasm after being treated with ebselen is determined by Western blot. (a) Ebselen decrased Bax level in cytoplasm in a concentration and time dependent manner. (b) Mitochondria Bax level increased and cytoplasmic Bax level decreased in MM cells treated with ebselen 40 μM for 4 hours. (c) The decreasing of cytoplasmic Bax level can be recovered partially by 15 mM NAC.
Mentions: Bax belongs to Bcl-2 family which is involved in apoptosis; there are some works which reported that Bax can be translocated to mitochondria after a cytotoxic stimulus [22]. So the next set of experiments were designed to find out if the Bax protein in MM cells behaved as others described after being treated with ebselen. Then we measured Bax by Western blot, including its expression and location. The result indicated that the Bax levels in the cytosol fraction were decreased after ebselen treatment in a concentration and time dependent manner (Figure 4(a)). After 40 μM ebselen treatment of MM cells for 4 hours, the Bax levels increased significantly in mitochondrial fraction and, in contrast, decreased in cytosol fraction (Figure 4(b)), which mean that ebselen can induce Bax translocation to mitochondria from cytosol.

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