Pyr3, a TRPC3 channel blocker, potentiates dexamethasone sensitivity and apoptosis in acute lymphoblastic leukemia cells by disturbing Ca2+ signaling, mitochondrial membrane potential changes and reactive oxygen species production

Abdoul-Azize, Souleymane; Buquet, Catherine; Vannier, Jean‐Pierre; Dubus, Isabelle

doi:10.1016/j.ejphar.2016.05.014

Cited by 22 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pyr3 has been reported to induce apoptosis in melanoma cells [5]. Pyr3 enhances Dex-induced apoptosis by increasing MMP depolarization in acute lymphoblastic leukemia cells [16]. Another TRPC blocker, SK&F96365, has been reported to induce apoptosis by increasing caspase-3/9 activity and MMP depolarization in A7r5 smooth muscle cells [17].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells

Chang

Cheng

Tsai

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Glioblastoma, also known as glioblastoma multiforme (GBM), is a fast-growing type of tumor that is the most aggressive brain malignancy in adults. According to GEO profile analysis, patients with high transient receptor potential canonical 3 (TRPC3) expression have poor survival rates. The aim of this study is to evaluate the effects of Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), a selective TRPC3 channel blocker, on the proliferation and migration of human glioblastoma cells. Methods: We first analyzed the TRPC3 mRNA expression in Gene Expression Omnibus (GEO) database. Then, TRPC3 protein expression was analyzed by Western blotting in three human GBM cell lines. The survival rate was measured by sulforhodamine B. JC1 staining was used to analyze the mitochondria membrane potential by flow cytometric analysis. Besides, the migration and invasion were evaluated by wound healing and Transwell assays. Annexin V and 7-aminoactinomycin D staining was used to monitor the apoptosis by flow cytometric analysis. The expression of apoptotic-related and migration-related proteins after Pyr3 treatment was detected by Western blotting. In addition, an orthotropic xenograft mouse model was used to assay the effect of Pyr3 in the in vivo study. Results: Basis on the results of bioinformatics study, glioma patients with higher TRPC3 expression had a shorter survival time than those with lower TRPC3 expression. GBM cell proliferation was decreased by Pyr3 treatment. The migration and invasion abilities of glioma cells were also inhibited via focal adhesion kinase and myosin light chain dephosphorization after Pyr3 treatment. Moreover, Pyr3 induced caspase-dependent apoptosis and mitochondria membrane potential imbalance in the GBM cells. In a xenograft animal model, Pyr3 in combination with temozolomide (TMZ) inhibited GBM tumor growth. Conclusion: Pyr3 inhibited GBM tumor growth in vitro and in vivo. Pyr3-TMZ combination therapy could be used to treat glioblastoma in the future.

show abstract

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells

Chang

Cheng

Tsai

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Dans des lignées de cellules leucé-miques, mais aussi dans des cellules primaires de patients atteints de leucémies, nous avons observé que Pyr3 bloque non seulement la libération du calcium à partir du réticulum endoplasmique, mais également l'influx calcique via les canaux calciques membranaires de manière dose-dépendante. Cette diminution du calcium intracellulaire induite par Pyr3 est corrélée à une diminution significative de la croissance des cellules leucémiques et aboutit à la mort cellulaire [8].…”

unclassified

“…Ces résultats renforcent donc l'hypothèse selon laquelle les GC amplifient la concentration intracellulaire du calcium. Dans un deuxième temps, nous avons montré, et ce pour la première fois, que la signalisation calcique induite par les GC est significativement diminuée en présence de Pyr3, l'inhibiteur du canal calcique TRPC3 [8].…”

unclassified

“…En combinaison avec les GC, Pyr3 déclenche une activité anti-leucémique de façon synergique et non additive. En effet, l'indice de combinaison 2 entre les deux médi-caments est nettement inférieur à un [8]. L'exploration des mécanismes pouvant réduire la viabilité des cellules LAL suite au traitement combiné GC et Pyr3 a permis de faire quatre observations : (1) un arrêt du cycle cellulaire en phase G2/M ; (2) une quantité importante de cellules apoptotiques en phase sous-G1 ; (3) une dissipation du potentiel transmembranaire mitochondrial ; et (4) Le co-traitement par des GC et Pyr3 de cellules de leucémies pédiatriques aiguës perturbe la signalisation calcique intracellulaire indispensable à la survie de ces cellules.…”

unclassified

“…Il en résulte un arrêt de la phase G2/M du cycle cellulaire et une augmentation de la mortalité cellulaire par apoptose. production de ROS (reactive oxygen species) [8]. L'ensemble de ces phénomènes conduit à l'apoptose cellulaire (Figure 1).…”

unclassified

See 2 more Smart Citations

Modulation de la sensibilité aux glucocorticoïdes dans les leucémies aiguës lymphoblastiques

Abdoul-Azize¹,

Dubus²,

Vannier³

2017

Med Sci (Paris)

Self Cite

View full text Add to dashboard Cite

Obesity‐induced mitochondrial dysfunction in porcine adipose tissue‐derived mesenchymal stem cells

Meng

Eirin

Zhu

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Transplantation of autologous mesenchymal stem cells (MSCs) may be a viable option for treatment of several diseases. MSCs efficacy depends on adequate function of their mitochondria, which might be impaired in a noxious milieu. We hypothesized that obesity compromises MSCs mitochondrial structure and function, possibly via micro-RNA (miRNA)-based mechanisms. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet (n = 7 each). Mitochondrial structure was assessed by electron microscopy and function by membrane potential and cytochrome-c oxidase (COX)-IV activity. Oxidative stress was assessed by Mito-SOX and dihydroethidium staining. Next-generation sequencing (RNA-seq) was performed to identify miRNAs expression in MSCs, and predicted mitochondrial target genes were then identified (MitoCarta). Compared to Lean-MSCs, mitochondria from Obese-MSCs were smaller and showed cristae remodeling and loss. Mitochondrial membrane potential and COX-IV activity decreased in Obese-MSCs, associated with increased mitochondrial oxidative stress. RNA-seq generated reads for 413 miRNAs, of which 5 miRNAs were upregulated in Obese-MSCs (fold change >2, p < 0.05) and found to target 43 specific mitochondrial genes. Obesity impairs MSC mitochondrial structure and function, possibly mediated partly through miRNA-induced mitochondrial gene regulation, leading to increased oxidative stress. Importantly, these alterations may limit the therapeutic use of autologous MSCs in subjects with obesity.

show abstract

Pyr3, a TRPC3 channel blocker, potentiates dexamethasone sensitivity and apoptosis in acute lymphoblastic leukemia cells by disturbing Ca2+ signaling, mitochondrial membrane potential changes and reactive oxygen species production

Cited by 22 publications

References 35 publications

Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells

Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells

Modulation de la sensibilité aux glucocorticoïdes dans les leucémies aiguës lymphoblastiques

Obesity‐induced mitochondrial dysfunction in porcine adipose tissue‐derived mesenchymal stem cells

Contact Info

Product

Resources

About