Anisomycin treatment enhances TRAIL-mediated apoptosis in renal carcinoma cells through the down-regulation of Bcl-2, c-FLIP(L) and Mcl-1

Seo, Bo Ram; Min, Kyoung‐jin; Kim, Shin; Park, Jong‐Wook; Park, Won-Kyun; Lee, Tae-Jin; Kwon, Taeg Kyu

doi:10.1016/j.biochi.2012.12.002

Cited by 25 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, the results demonstrated the roles of apoptotic proteins in inhibition of alsterpaullone on HeLa cells. Mcl-1 is a short-lived protein because the PEST sequences present with the Bcl-2 family member, and it is an important anti-apoptotic protein [13, 14]. In the current study, we found that Mcl-1 protein was rapidly down-regulated and even undetectable as early as 2 h in HeLa cells.…”

Section: Discussionsupporting

confidence: 53%

Alsterpaullone, a Cyclin-Dependent Kinase Inhibitor, Mediated Toxicity in HeLa Cells through Apoptosis-Inducing Effect

Cui

Wang

et al. 2013

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

Alsterpaullone, a small molecule cyclin-dependent kinase (CDK) inhibitor, regulates the cell cycle progression. Beyond death-inducing properties, we identified the effect of alsterpaullone on cycle procedure and apoptosis of HeLa cell. It was found that alsterpaullone inhibited HeLa cells in a time-dependent (0–72 h) and dose-dependent (0–30 μM) manner. In the presence of alsterpaullone, HeLa cells were arrested in G2/M prior to undergoing apoptosis via a mechanism that is involved in the regulation of various antiapoptotic genes, DNA-repair, transcription, and cell cycle progression. Compared to controls, alsterpaullone effectively prevented HeLa cells from entering S-phase. These potential therapeutic efficacies could be correlated with the activation of caspase-3.

show abstract

Section: Discussionsupporting

confidence: 53%

Alsterpaullone, a Cyclin-Dependent Kinase Inhibitor, Mediated Toxicity in HeLa Cells through Apoptosis-Inducing Effect

Cui

Wang

et al. 2013

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

show abstract

“…Alternatively increased expression of the anti-apoptotic protein c-FLIP can function upstream of caspase-8 to decrease apoptosis signaling [73]. Interestingly c-FLIP shows variable expression depending on tumor type and may represent a key mechanism of TRAIL-specific tumor escape [74,75,76]. Alternative mechanisms for resistance to TRAIL-mediated apoptosis includes the overexpression of the anti-apoptotic proteins Bcl-2 and Bcl-XL, both of which function to prevent mitochondrial release of cytochrome C and activation of the intrinsic apoptosis pathway [77,78].…”

Section: Modulation Of Tumor Necrosis Factor (Tnf)-related Apoptosmentioning

confidence: 99%

Regulation of TRAIL-Receptor Expression by the Ubiquitin-Proteasome System

Sarhan

D’Arcy

Lundqvist

2014

IJMS

View full text Add to dashboard Cite

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand- receptor (TRAIL-R) family has emerged as a key mediator of cell fate and survival. Ligation of TRAIL ligand to TRAIL-R1 or TRAIL-R2 initiates the extrinsic apoptotic pathway characterized by the recruitment of death domains, assembly of the death-inducing signaling complex (DISC), caspase activation and ultimately apoptosis. Conversely the decoy receptors TRAIL-R3 and TRAIL-R4, which lack the pro-apoptotic death domain, function to dampen the apoptotic response by competing for TRAIL ligand. The tissue restricted expression of the decoy receptors on normal but not cancer cells provides a therapeutic rational for the development of selective TRAIL-mediated anti-tumor therapies. Recent clinical trials using agonistic antibodies against the apoptosis-inducing TRAIL receptors or recombinant TRAIL have been promising; however the number of patients in complete remission remains stubbornly low. The mechanisms of TRAIL resistance are relatively unexplored but may in part be due to TRAIL-R down-regulation or shedding of TRAIL-R by tumor cells. Therefore a better understanding of the mechanisms underlying TRAIL resistance is required. The ubiquitin-proteasome system (UPS) has been shown to regulate TRAIL-R members suggesting that pharmacological inhibition of the UPS may be a novel strategy to augment TRAIL-based therapies and increase efficacies. We recently identified b-AP15 as an inhibitor of proteasome deubiquitinase (DUB) activity. Interestingly, exposure of tumor cell lines to b-AP15 resulted in increased TRAIL-R2 expression and enhanced sensitivity to TRAIL-mediated apoptosis and cell death in vitro and in vivo. In conclusion, targeting the UPS may represent a novel strategy to increase the cell surface expression of pro-apoptotic TRAIL-R on cancer cells and should be considered in clinical trials targeting TRAIL-receptors in cancer patients.

show abstract

“…Yu et al (9) found that anisomycin inhibited the proliferation of Jurkat T cells by promoting the expression of p53, p21 and p27, thus stopping the cells from entering the S and G2/M phases. Seo et al (10) reported that anisomycin could induce apoptosis in renal tumour cells by downregulating Bcl-2, c-FLIPL and Mcl-1. Liu et al (11) also demonstrated that anisomycin induced the apoptosis of cancer cells in glucocorticoid-resistant acute lymphoblastic leukaemia by facilitating the phosphorylation of the mitogen-activated protein kinase p38 and the activation of JNK.…”

Section: Introductionmentioning

confidence: 99%

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

Shen

et al. 2019

Int J Oncol

View full text Add to dashboard Cite

Angiogenesis has an important role in tumour cell growth and metastasis. Anisomycin has been shown to inhibit tumour cell growth. However, whether anisomycin can inhibit angiogenesis of tumours has not been reported. The present study demonstrated that there was a positive correlation between tumour angiogenesis and the number of CD44 + /CD133 + serous human ovarian cancer stem cells (HuOCSCs). Subsequently, it was confirmed that anisomycin significantly inhibited the proliferation, invasion, tumorigenic ability and tumour angiogenesis of HuOCSCs. Gene expression profiling by cDNA microarrays revealed that the expression levels of vascular endothelial cell markers, platelet-derived growth factors, Notch pathway components and 27 tumour angiogenesis-related genes were significantly decreased in the anisomycin-treated group compared with the control group. Further experiments demonstrated that the expression levels of endogenous long non-coding RNA (lncRNA) maternally expressed 3 (Meg3) were significantly decreased in anisomycin-treated HuOCSCs, whereas the expression levels of microRNA (miR)-421 were significantly increased. The results of luciferase reporter assays indicated that, when miR-421 was overexpressed in cells, the luciferase activities of wild-type platelet derived growth factor receptor α (PDGFRA) 3' untranslated region and Meg3 reporter plasmids were significantly decreased. Overexpression of miR-421 in HuOCSCs significantly enhanced the anisomycin-mediated inhibition of HuOCSC proliferation. Taken together, the present results demonstrated that anisomycin inhibited the activation downstream of the Notch1 pathway by attenuating the molecular sponge effect of the lncRNA-Meg3/miR-421/PDGFRA axis, ultimately inhibiting angiogenesis, proliferation and invasion in ovarian cancer cells.

show abstract

Anisomycin treatment enhances TRAIL-mediated apoptosis in renal carcinoma cells through the down-regulation of Bcl-2, c-FLIP(L) and Mcl-1

Cited by 25 publications

References 25 publications

Alsterpaullone, a Cyclin-Dependent Kinase Inhibitor, Mediated Toxicity in HeLa Cells through Apoptosis-Inducing Effect

Alsterpaullone, a Cyclin-Dependent Kinase Inhibitor, Mediated Toxicity in HeLa Cells through Apoptosis-Inducing Effect

Regulation of TRAIL-Receptor Expression by the Ubiquitin-Proteasome System

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

Contact Info

Product

Resources

About