Limits...
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 stimulated the activities of caspase-3 and -9 of WEHI-3 cells. Cells were seeded in RPMI 1640 medium + 10% FBS with pretreatment with NAC,  inhibitors of caspase-9 and -3 or a pan-caspase inhibitor, and then were exposed to 100 μM of emodin for 24 h. Cells were determined the caspase-3, -8, and -9 activity (a) and percentage of viable cells (b) as described in Section 2. Each experiment was done with triple sets, and columns, mean of three determinations; bars, SD. *P < .05 and ***P < .001 were considered significant different as compared to the DMSO-treated control group.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3108103&req=5

fig4: Emodin stimulated the activities of caspase-3 and -9 of WEHI-3 cells. Cells were seeded in RPMI 1640 medium + 10% FBS with pretreatment with NAC, inhibitors of caspase-9 and -3 or a pan-caspase inhibitor, and then were exposed to 100 μM of emodin for 24 h. Cells were determined the caspase-3, -8, and -9 activity (a) and percentage of viable cells (b) as described in Section 2. Each experiment was done with triple sets, and columns, mean of three determinations; bars, SD. *P < .05 and ***P < .001 were considered significant different as compared to the DMSO-treated control group.

Mentions: In order to evaluate the roles of caspase-mediated pathways in emodin-induced apoptotic death of WEHI-3 cells, cells were pretreated with a pan-caspase inhibitor (Z-VAD-FMK), and then exposed to emodin. We found that emodin promoted the activities of caspase-3 and -9, but it did not affect that of caspase-8 (Figure 4(a)). Pretreatment with Z-VAD-FMK could decrease emodin-stimulated the activities of caspase-3 and -9 in WEHI-3 cells (Figure 4(a)). Furthermore, cells were individually preincubated with an antioxidant scavenger (NAC), caspase-9 inhibitor (Z-IETD-FMK), and caspase-3 inhibitor (Z-DEVD-FMK), which led to increase emodin-reduced the percentage of viable WEHI-3 cells compared to the emodin-treated cells only (Figure 4(b)). These data suggest that emodin triggered apoptosis of WEHI-3 cells through the ROS and caspase-dependent pathways.


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 stimulated the activities of caspase-3 and -9 of WEHI-3 cells. Cells were seeded in RPMI 1640 medium + 10% FBS with pretreatment with NAC,  inhibitors of caspase-9 and -3 or a pan-caspase inhibitor, and then were exposed to 100 μM of emodin for 24 h. Cells were determined the caspase-3, -8, and -9 activity (a) and percentage of viable cells (b) as described in Section 2. Each experiment was done with triple sets, and columns, mean of three determinations; bars, SD. *P < .05 and ***P < .001 were considered significant different as compared to the DMSO-treated control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Emodin stimulated the activities of caspase-3 and -9 of WEHI-3 cells. Cells were seeded in RPMI 1640 medium + 10% FBS with pretreatment with NAC, inhibitors of caspase-9 and -3 or a pan-caspase inhibitor, and then were exposed to 100 μM of emodin for 24 h. Cells were determined the caspase-3, -8, and -9 activity (a) and percentage of viable cells (b) as described in Section 2. Each experiment was done with triple sets, and columns, mean of three determinations; bars, SD. *P < .05 and ***P < .001 were considered significant different as compared to the DMSO-treated control group.
Mentions: In order to evaluate the roles of caspase-mediated pathways in emodin-induced apoptotic death of WEHI-3 cells, cells were pretreated with a pan-caspase inhibitor (Z-VAD-FMK), and then exposed to emodin. We found that emodin promoted the activities of caspase-3 and -9, but it did not affect that of caspase-8 (Figure 4(a)). Pretreatment with Z-VAD-FMK could decrease emodin-stimulated the activities of caspase-3 and -9 in WEHI-3 cells (Figure 4(a)). Furthermore, cells were individually preincubated with an antioxidant scavenger (NAC), caspase-9 inhibitor (Z-IETD-FMK), and caspase-3 inhibitor (Z-DEVD-FMK), which led to increase emodin-reduced the percentage of viable WEHI-3 cells compared to the emodin-treated cells only (Figure 4(b)). These data suggest that emodin triggered apoptosis of WEHI-3 cells through the ROS and caspase-dependent pathways.

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