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Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo.

Chang YC, Lai TY, Yu CS, Chen HY, Yang JS, Chueh FS, Lu CC, Chiang JH, Huang WW, Ma CY, Chung JG - Evid Based Complement Alternat Med (2011)

Bottom Line: Emodin stimulated the productions of ROS and Ca(2+) and reduced the level of ΔΨ(m) by flow cytometry.Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways.In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.

ABSTRACT
Emodin is one of major compounds in rhubarb (Rheum palmatum L.), a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3) and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca(2+) and reduced the level of ΔΨ(m) by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

No MeSH data available.


Related in: MedlinePlus

Emodin affected the levels of ROS, Ca2+ and ΔΨm in WEHI-3 cells. Cells were cultured in 100 μM emodin for 0, 1, 3, 6, 12 or 24 h. Cells were harvested and resuspended in DCFH-DA for determining the changes in ROS (a), in Fluo-3/AM for staining of Ca2+ (b) and in DiOC6 for determining ΔΨm (c) as described in Section 2. *P < .05 and ***P < .001 were considered significant when compared with DMSO-treated control.
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fig3: Emodin affected the levels of ROS, Ca2+ and ΔΨm in WEHI-3 cells. Cells were cultured in 100 μM emodin for 0, 1, 3, 6, 12 or 24 h. Cells were harvested and resuspended in DCFH-DA for determining the changes in ROS (a), in Fluo-3/AM for staining of Ca2+ (b) and in DiOC6 for determining ΔΨm (c) as described in Section 2. *P < .05 and ***P < .001 were considered significant when compared with DMSO-treated control.

Mentions: Cells treated with 100 μM emodin were determined by flow cytometric assays and results are shown in Figures 3(a), 3(b), and 3(c), which indicated that emodin promoted the levels of ROS (Figure 3(a)) and Ca2+(Figure 3(b)), but decreased the level of ΔΨm (Figure 3(c)). To investigate emodin-induced cell death is through the disruption of mitochondrial respiratory chain, leading to ROS accumulation and cellular damage. An increase in intracellular fluorescence after DCFH-DA loading showed the reversal of ROS accumulation (Figure 3(a)). In order to elucidate the mechanism of emodin-induced mitochondria-dependent apoptotic cell death, the effects of emodin on the levels of intracellular Ca2+ and ΔΨm were analyzed. These data indicated that emodin-induced apoptosis is possibly mediated through alteration of mitochondrial permeability transition in WEHI-3 cells in vitro.


Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo.

Chang YC, Lai TY, Yu CS, Chen HY, Yang JS, Chueh FS, Lu CC, Chiang JH, Huang WW, Ma CY, Chung JG - Evid Based Complement Alternat Med (2011)

Emodin affected the levels of ROS, Ca2+ and ΔΨm in WEHI-3 cells. Cells were cultured in 100 μM emodin for 0, 1, 3, 6, 12 or 24 h. Cells were harvested and resuspended in DCFH-DA for determining the changes in ROS (a), in Fluo-3/AM for staining of Ca2+ (b) and in DiOC6 for determining ΔΨm (c) as described in Section 2. *P < .05 and ***P < .001 were considered significant when compared with DMSO-treated control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108103&req=5

fig3: Emodin affected the levels of ROS, Ca2+ and ΔΨm in WEHI-3 cells. Cells were cultured in 100 μM emodin for 0, 1, 3, 6, 12 or 24 h. Cells were harvested and resuspended in DCFH-DA for determining the changes in ROS (a), in Fluo-3/AM for staining of Ca2+ (b) and in DiOC6 for determining ΔΨm (c) as described in Section 2. *P < .05 and ***P < .001 were considered significant when compared with DMSO-treated control.
Mentions: Cells treated with 100 μM emodin were determined by flow cytometric assays and results are shown in Figures 3(a), 3(b), and 3(c), which indicated that emodin promoted the levels of ROS (Figure 3(a)) and Ca2+(Figure 3(b)), but decreased the level of ΔΨm (Figure 3(c)). To investigate emodin-induced cell death is through the disruption of mitochondrial respiratory chain, leading to ROS accumulation and cellular damage. An increase in intracellular fluorescence after DCFH-DA loading showed the reversal of ROS accumulation (Figure 3(a)). In order to elucidate the mechanism of emodin-induced mitochondria-dependent apoptotic cell death, the effects of emodin on the levels of intracellular Ca2+ and ΔΨm were analyzed. These data indicated that emodin-induced apoptosis is possibly mediated through alteration of mitochondrial permeability transition in WEHI-3 cells in vitro.

Bottom Line: Emodin stimulated the productions of ROS and Ca(2+) and reduced the level of ΔΨ(m) by flow cytometry.Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways.In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.

ABSTRACT
Emodin is one of major compounds in rhubarb (Rheum palmatum L.), a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3) and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca(2+) and reduced the level of ΔΨ(m) by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

No MeSH data available.


Related in: MedlinePlus