Apoptosis of Bone Marrow Mesenchymal Stem Cells Caused by Homocysteine via Activating JNK Signal

Cai, Benzhi; Li, Xingda; Wang, Yang; Liu, Yanju; Yang, Fan; Chen, Hongyang; Yin, Kun; Tan, Xueying; Zhu, Jiuxin; Pan, Zhenwei; Wang, Baoqiu; Lu, Yanjie

doi:10.1371/journal.pone.0063561

Cited by 37 publications

(29 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several recent reports have suggested that MAPKs such as ERK1/2 and JNK MAPK exert their roles in response to various apoptotic stimuli (19,20). Figure 2E shows that quercetin promoted pronounced ERK1/2 and JNK phosphorylation in a dose-dependent manner after 24-hour treatment.…”

Section: Resultsmentioning

confidence: 79%

Multitarget Effects of Quercetin in Leukemia

Maso

Calgarotto

Franchi

et al. 2014

Cancer Prevention Research

View full text Add to dashboard Cite

This study proposes to investigate quercetin antitumor efficacy in vitro and in vivo, using the P39 cell line as a model. The experimental design comprised leukemic cells or xenografts of P39 cells, treated in vitro or in vivo, respectively, with quercetin; apoptosis, cell-cycle and autophagy activation were then evaluated. Quercetin caused pronounced apoptosis in P39 leukemia cells, followed by Bcl-2, Bcl-xL, Mcl-1 downregulation, Bax upregulation, and mitochondrial translocation, triggering cytochrome c release and caspases activation. Quercetin also induced the expression of FasL protein. Furthermore, our results demonstrated an antioxidant activity of quercetin. Quercetin treatment resulted in an increased cell arrest in G 1 phase of the cell cycle, with pronounced decrease in CDK2, CDK6, cyclin D, cyclin E, and cyclin A proteins, decreased Rb phosphorylation and increased p21 and p27 expression. Quercetin induced autophagosome formation in the P39 cell line. Autophagy inhibition induced by quercetin with chloroquine triggered apoptosis but did not alter quercetin modulation in the G 1 phase. P39 cell treatment with a combination of quercetin and selective inhibitors of ERK1/2 and/or JNK (PD184352 or SP600125, respectively), significantly decreased cells in G 1 phase, this treatment, however, did not change the apoptotic cell number. Furthermore, in vivo administration of quercetin significantly reduced tumor volume in P39 xenografts and confirmed in vitro results regarding apoptosis, autophagy, and cell-cycle arrest. The antitumor activity of quercetin both in vitro and in vivo revealed in this study, point to quercetin as an attractive antitumor agent for hematologic malignancies. Cancer Prev Res; 7(12); 1240-50. Ó2014 AACR.

show abstract

Section: Resultsmentioning

confidence: 79%

Multitarget Effects of Quercetin in Leukemia

Maso

Calgarotto

Franchi

et al. 2014

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…BMSCs apoptosis was detected using acridine orange/ethidium bromide (AO/EB) staining [19]. The cultured BMSCs were treated with different concentrations of doxorubicin for 48 h. In order to label the apoptotic cells, 10 μL prepared AO/EB working solution (100 μg/mL AO and 100 μg/mL EB in PBS) was added to the cells for 5 min.…”

Section: Methodsmentioning

confidence: 99%

“…Effects of doxorubicin on BMSCs apoptosis were determined using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay as described previously [19]. The cultured BMSCs were fixed with 4% paraformaldehyde for 1 h at room temperature, blocked and then permeabilized in 0.1% Triton X-100.…”

Section: Methodsmentioning

confidence: 99%

Doxorubicin Caused Apoptosis of Mesenchymal Stem Cells via p38, JNK and p53 Pathway

Yang

Chen

Liu

et al. 2013

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Doxorubicin is a widely used chemotherapeutic agent, but its clinical use is restricted because of a high risk of cardiotoxicity. Bone marrow-derived mesenchymal stem cells (BMSCs) may repair ischaemically damaged myocardium through transdifferentiation and paracrine action. The aim of this study is to investigate if doxorubicin causes the apoptosis of BMSCs and in turn impairs its healing ability. Methods: BMSCs were exposed to doxorubicin, and cell apoptosis was determined by western blot and stainings. Results: Doxorubicin reduced the survival ratio and caused the apoptosis of BMSCs, with the increase of intracellular ROS level and depolarization of mitochondrial membrane potential. The ROS scavenger NAC abrogated these consequences. Moreover, doxorubicin markedly activated phosphorylated ERK, p38 and JNK proteins in BMSCs. The specific inhibitors for p38 (SB203580) and JNK (SP600125) may abolish doxorubicin-induced apoptosis of BMSCs but the specific ERK inhibitor (PD98059) not, indicating p38 and JNK activation contribute to BMSCs apoptosis. Also, the phosphorylated and total p53 proteins were increased in doxorubicin-treated BMSCs. Proapoptotic cleaved caspases-3 was upregulated and antiapoptotic Bcl-2 protein was reduced in doxorubicin-treated BMSCs. At last, ELISA assay showed that doxorubicin treatment reduced the VEGF and IGF-1 released by BMSCs. Conclusion: Taken together, doxorubicin caused BMSCs apoptosis associated with p38, JNK and p53 pathways.

show abstract

“…It has been reported that ROS production regulates aging, senescence, and osteogenic differentiation in mesenchymal stem cells [23,24]. To further evaluate the effects of blue LED irradiation on ROS production, we performed DCF-DA staining in blue LED treated and untreated BMSCs.…”

Section: Increased Intracellular Reactive Oxygen Species (Ros) Levelsmentioning

confidence: 99%

Effects of Blue Light Emitting Diode Irradiation On the Proliferation, Apoptosis and Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

Yuan

Yan

Gong

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrowderived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS

show abstract

Apoptosis of Bone Marrow Mesenchymal Stem Cells Caused by Homocysteine via Activating JNK Signal

Cited by 37 publications

References 41 publications

Multitarget Effects of Quercetin in Leukemia

Multitarget Effects of Quercetin in Leukemia

Doxorubicin Caused Apoptosis of Mesenchymal Stem Cells via p38, JNK and p53 Pathway

Effects of Blue Light Emitting Diode Irradiation On the Proliferation, Apoptosis and Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

Contact Info

Product

Resources

About