Bone marrow mesenchymal stem cells suppress growth and promote the apoptosis of glioma U251 cells through downregulation of the PI3K/AKT signaling pathway

Lü, Li; Chen, Guohu; Yang, Jingjing; Ma, Zhanjun; Yang, Yang; Yan, Hu; Lu, Yubao; Cao, Zhang-Qi; Wang, Yan; Wang, Xuexi

doi:10.1016/j.biopha.2019.108625

Cited by 67 publications

(45 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PI3K/AKT signaling molecule, as one of the important pathways regulating cell proliferation, is also involved in cell apoptosis (48). It has reported that the phosphorylation of BAD is inhibited by PI3K/Akt signaling molecules, resulting in cell apoptosis (49).…”

Section: Discussionmentioning

confidence: 99%

Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells

Pan

Zhang

et al. 2019

Front. Oncol.

View full text Add to dashboard Cite

Emerging evidence has shown that cinobufagin, as an active ingredient of Venenum Bufonis, inhibits tumor development. The aim of this study was to investigate the inhibitory effects of cinobufagin on A375 human malignant melanoma cells. MTT and colony formation assays showed that cinobufagin significantly inhibited A375 cell proliferation and cell colony formation. Additional studies demonstrated that cinobufagin markedly increased the levels of ATM serine/threonine kinase (ATM) and checkpoint kinase 2 (Chk2) and decreased the levels of cell division cycle 25C (CDC25C), cyclin-dependent kinase 1 (CDK1), and cyclin B, subsequently inducing G2/M cell cycle arrest in A375 cells. Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2). By contrast, it increased the levels of Bcl-2-associated death promoter, Bcl-2-associated X, cytoplasmic cytochrome C, and apoptotic protease activating factor 1, leading to increased levels of cleaved caspase-9 and cleaved caspase-3, resulting in the apoptosis of A375 cells. Together, these results indicate that cinobufagin can induce cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of A375/B16 cell proliferation. Thus, cinobufagin may be useful for melanoma treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells

Pan

Zhang

et al. 2019

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…The interaction of MSCs with tumor cell cycle is the most commonly accepted process by which MSCs exert their therapeutic effects (Fathi et al, 2019). By inhibiting proliferation-related signaling pathways, such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), MSCs can induce cell cycle arrest and reduce cancer growth (Lu et al, 2019). In addition, MSCs can undergo differentiation into other cell types, such as cancerassociated fibroblasts (CAFs), to directly contribute to cancer progression (Jotzu et al, 2011;Barcellos-de-Souza et al, 2016;Aoto et al, 2018) (Figure 3).…”

Section: Divergent Roles Of Mscs In Cancer Treatmentmentioning

confidence: 99%

“…Previous studies have demonstrated that MSCs release cytotoxic agents, such as TNF-Related Apoptosis-Inducing Ligand (TRAIL) that selectively induces apoptosis in different types of cancer (Wiley et al, 1995;Hao et al, 2001;Takeda et al, 2001;Akimoto et al, 2013). Recently, a report indicated that bone marrow MSCs promote apoptosis and suppress growth of glioma U251 cells through downregulation of the PI3K/AKT signaling pathway (Lu et al, 2019). Similarly, intravenously transplanted MSCs were found to suppress tumor growth by blocking AKT activation in a Kaposi sarcoma mouse model (Khakoo et al, 2006).…”

Section: Anti-tumor Activitymentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

Hmadcha

Martín-Montalvo

Gauthier

et al. 2020

Front. Bioeng. Biotechnol.

275

204

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSCbased therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.

show abstract

“…The 2-DE analysis was performed as described previously [32,33]. Briefly, 100 mg of spinal cord tissue (SCI group and SCI + 20 mg/kg RA group) were harvested and lysed in 1 mL of lysis buffer.…”

Section: -De and Imaging Analysesmentioning

confidence: 99%

“…8.0.1; Bio-Rad Laboratories). Protein spots were extracted from the 2-DE gels and identified by MALDI-TOF/MS, and protein-protein interaction network and gene ontology (GO) analyses of differential proteins were performed as described previously [32,33].…”

Section: -De and Imaging Analysesmentioning

confidence: 99%

Rosmarinic acid exerts a neuroprotective effect on spinal cord injury by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways

Bone marrow mesenchymal stem cells suppress growth and promote the apoptosis of glioma U251 cells through downregulation of the PI3K/AKT signaling pathway

Cited by 67 publications

References 42 publications

Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells

Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells

Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

Rosmarinic acid exerts a neuroprotective effect on spinal cord injury by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways

Contact Info

Product

Resources

About