FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma cells

Zhang, Li; Wang, Handong; Ding, Ke; Xu, Jianguo

doi:10.1016/j.toxlet.2015.04.015

Cited by 64 publications

(71 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies have demonstrated that S1P is a survival factor in various cell types, including intestinal and follicular cells and prostate adenocarcinoma [60]. In addition, there is evidence that FTY720, a nonselective sphingosine-1-phosphate (S1P) receptor modulator, causes apoptosis of lymphocytes and tumor cells [61,62]. Despite evidence suggesting that FTY720 also induces atypical cell death in human neutrophils associated with cell swelling and vacuolization by sphingosine-1-phosphate receptors-independent mechanism [63], our data showed that FTY720 induced morphological alteration associated to apoptosis [64] in neutrophil and induced cleavage of caspase 3, a hallmark of this type of cell death [65][66][67].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the sphingosine‐1‐phosphate pathway promotes the resolution of neutrophilic inflammation

et al. 2019

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and the blockade of S1P synthesis in BALB/c mice and human neutrophils. S1P and S1PR1-3 receptors expression were increased in cells from the pleural cavity stimulated with LPS. Using different antagonists of S1PRs and inhibitors of different steps of the metabolic pathway of S1P production, we show that S1P and its receptors are involved in regulating neutrophil survival and resolution of inflammation in the pleural cavity. Given the role of the S1P-S1PR axis in resolution of inflammation, we sought to identify whether blockade at different levels of the sphingosine-1-phosphate synthesis pathway could affect neutrophil survival in vitro. Inhibitors of the S1P pathway were also able to induce human neutrophil apoptosis. In addition, blockade of S1P synthesis or its receptor facilitated the efferocytosis of apoptotic neutrophil. Taken together, our data demonstrate a fundamental role for S1P in regulating the outcome of inflammatory responses, and position S1P-S1PR axis as a potential target for treatment of neutrophilic inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of the sphingosine‐1‐phosphate pathway promotes the resolution of neutrophilic inflammation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…For example, FTY720 was shown to induce autophagy via a ROS-dependent mechanism, which promoted apoptosis in multiple myeloma cells 27 . This autophagy-related apoptosis was also reported to increase in FTY720-treated glioblastoma cells 24 . However, FTY720-mediated autophagy does not always lead to apoptosis, as autophagic flux in ovarian cancer cells induced by FTY-720 plays a cyto-protective role 10 .…”

Section: Discussionmentioning

confidence: 63%

“…In light of several reports that FTY720 induces autophagy in glioblastoma cells and ovarian cancer cells 10, 24 , we further investigated the potential interplay between autophagy and FTY720-mediated antitumor effects. Transmission electron microscopy revealed the ability of FTY720 to induce the formation of autophagosomes (arrow) in the cytoplasm, indicative of autophagy (Fig.…”

Section: Resultsmentioning

confidence: 99%

FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism

Chiu

et al. 2017

Sci Rep

View full text Add to dashboard Cite

In this study, we interrogated the mechanism by which the immunosuppressant FTY720 mediates anticancer effects in oral squamous cell carcinoma (OSCC) cells. FTY720 differentially suppressed the viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC50 values of 6.1, 6.3, and 4.5 μM, respectively. This antiproliferative effect was attributable to the ability of FTY720 to induce caspase-dependent apoptosis. Mechanistic evidence suggests that FTY720-induced apoptosis was associated with its ability to inhibit Akt-NF-κB signaling, to facilitate the proteasomal degradation of the antiapoptotic protein Mcl-1, and to increase reactive oxygen species (ROS) generation. Both overexpression of Mcl-1 and inhibition of ROS partially protected cells from FTY720-induced caspase-9 activation, PARP cleavage and cytotoxicity. In addition, FTY720 induced autophagy in OSCC cells, as manifested by LC3B-II conversion, decreased p62 expression, and accumulation of autophagosomes. Inhibition of autophagy by bafilomycin A1 protected cells from FTY720-induced apoptosis. Together, these findings suggest an intricate interplay between autophagy and apoptosis in mediating the tumor-suppressive effect in OSCC cells, which underlies the translational potential of FTY720 in fostering new therapeutic strategies for OSCC.

show abstract

“…On the other hand, PDT is known to induce both necrosis and apoptosis in glioblastoma [19,20]. Recently, Receptor Interacting Protein kinase 3 (RIP3), a key protein of the programmed necrosis pathway (necroptosis) was demonstrated to be involved in PDT-induced glioblastoma cell death induced by PDT [21][22][23] and other cell death inducers [24][25][26]. The current model of necroptosis relies on the assembly of the "necrosome" complex, in which Receptor Interacting Protein kinase 3 (RIP3) interacts with RIP1, Fas-Associated protein with Death Domain (FADD) and Caspase-8 upon a combined treatment of TNF-α, Smac-mimetic and pan-caspases inhibitors [27].…”

Section: Introductionmentioning

confidence: 99%

RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death

Fettweis¹,

Valentin

L’homme³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Glioblastomas are the deadliest type of brain cancer and are frequently associated with poor prognosis and a high degree of recurrence despite removal by surgical resection and treatment by chemo-and radio-therapy. Photodynamic therapy (PDT) is a treatment well known to induce mainly necrotic and apoptotic cell death in solid tumors. 5-Aminolevulinic acid (5-ALA)-based PDT was recently shown to sensitize human glioblastoma cells (LN-18) to a RIP3 (Receptor Interacting Protein 3)-dependent cell death which is counter-acted by activation of autophagy. These promising results led us to investigate the pathways involved in cell death and survival mechanisms occurring in glioblastoma following PDT. In the present study, we describe a new TSC2 (Tuberous Sclerosis 2)-dependent survival pathway implicating MK2 (MAPKAPK2) kinase and 14-3-3 proteins which conducts to the activation of a pro-survival autophagy. Moreover, we characterized a new RIP3/TSC2 complex where RIP3 is suggested to promote cell death by targeting TSC2-dependent survival pathway. These results highlight (i) a new role of TSC2 to protect glioblastoma against PDT-induced cell death and (ii) TSC2 and 14-3-3 as new RIP3 partners.

show abstract

FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma cells

Cited by 64 publications

References 61 publications

Inhibition of the sphingosine‐1‐phosphate pathway promotes the resolution of neutrophilic inflammation

Inhibition of the sphingosine‐1‐phosphate pathway promotes the resolution of neutrophilic inflammation

FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism

RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death

Contact Info

Product

Resources

About