Synergistic Inhibition of Survival, Proliferation, and Migration of U87 Cells with a Combination of LY341495 and Iressa

Zhang, Liying; Carrillo, Vangie; Dubisz, Ewa; Gulzar, Hira; Morgan, Devon; Mahajan, Shahana S.

doi:10.1371/journal.pone.0064588

Cited by 33 publications

(33 citation statements)

References 50 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell proliferation was quantified by determining the fluorescence of DAPI depending on cell density using the fluorescence microscopy. At least four locations were selected to calculate the average cell density; the fluorescence intensity of DAPI was measured using Image J Pro software (Yelskaya et al, ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Wnt3A Induces GSK‐3β Phosphorylation and β‐Catenin Accumulation Through RhoA/ROCK

Kim

Choi

et al. 2016

Journal Cellular Physiology

View full text Add to dashboard Cite

In canonical pathway, Wnt3A has been known to stabilize β-catenin through the dissociation between β-catenin and glycogen synthase kinase-3β (GSK-3β) that suppresses the phosphorylation and degradation of β-catenin. In non-canonical signaling pathway, Wnt was known to activate Rho GTPases and to induce cell migration. The cross-talk between canonical and non-canonical pathways by Wnt signaling; however, has not been fully elucidated. Here, we revealed that Wnt3A induces not only the phosphorylation of GSK-3β and accumulation of β-catenin but also RhoA activation in RAW264.7 and HEK293 cells. Notably, sh-RhoA and Tat-C3 abolished both the phosphorylation of GSK-3β and accumulation of β-catenin. Y27632, an inhibitor of Rho-associated coiled coil kinase (ROCK) and si-ROCK inhibited both GSK-3β phosphorylation and β-catenin accumulation. Furthermore, active domain of ROCK directly phosphorylated the purified recombinant GSK-3β in vitro. In addition, Wnt3A-induced cell proliferation and migration, which were inhibited by Tat-C3 and Y27632. Taken together, we propose the cross-talk between canonical and non-canonical signaling pathways of Wnt3A, which induces GSK-3β phosphorylation and β-catenin accumulation through RhoA and ROCK activation. J. Cell. Physiol. 232: 1104-1113, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Methodsmentioning

confidence: 99%

“…At least four locations were selected to calculate the average cell density; the fluorescence intensity of DAPI was measured using Image J Pro software (Yelskaya et al, 2013).…”

Section: Cell Proliferation Measurementmentioning

confidence: 99%

Wnt3A Induces GSK‐3β Phosphorylation and β‐Catenin Accumulation Through RhoA/ROCK

Kim

Choi

et al. 2016

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…However, pharmacological studies revealed also the antitumour and/or chemosensitizing potential of mGluR1 (e.g. Bay 36‐7620, YM 298198) and group II mGluR (LY341495) antagonists . Among mGluRs, the group III still remains not fully explored in relation to its role in cancer .…”

mentioning

confidence: 99%

Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic‐Induced Human Neuroblastoma SH‐SY5Y Cell Damage: The Impact of Cell Differentiation State

Jantas

Grygier

Zatorska

et al. 2018

Basic Clin Pharma Tox

View full text Add to dashboard Cite

The participation of group III metabotropic glutamate receptors (mGluRs) in cancer growth and progression is still an understudied issue. Based on our recent data on high expression of mGluR8 in human neuroblastoma SH-SY5Y cells, in this study, we evaluated the effect of an mGluR8-specific positive allosteric modulator (PAM: AZ12216052) and orthosteric agonist [(S)-3,4-DCPG ((S)-3,4-dicarboxyphenylglycine)] on chemotherapeutic (doxorubicin, irinotecan or cisplatin)-evoked cell damage in undifferentiated (UN-) and retinoic acid-differentiated (RA-) SH-SY5Y cells. The data showed that AZ12216052 as well as a group III mGluR antagonist (UBP1112) but not (S)-3,4-DCPG partially inhibited the cell damage evoked by doxorubicin, irinotecan or cisplatin in UN-SH-SY5Y cells. In RA-SH-SY5Y, we observed only a modest protective effect of mGluR8 PAM. In contrast, both types of mGluR8 activators significantly enhanced toxic effects of doxorubicin and irinotecan in RA-SH-SY5Y cells. These data suggest that in undifferentiated neuroblastoma malignant cells, some mGluR8 modulators can decrease cytotoxic effects of chemotherapeutics which exclude them from the group of putative anticancer agents. On the other hand, in SH-SY5Y cells differentiated to a more mature neuron-like phenotype, that is non-malignant cells, the mGluR8 activators can aggravate the chemotherapeutic neurotoxicity which is a well-known undesired effect of these drugs. Our pharmacological data add new observations to the unexplored field of research on the role of mGluR8 in cancer, pointing to complexity of response which could be mediated by particular types of mGluR8 ligands at least in neuroblastoma cells.

show abstract

“…Nowadays, the insufficiency of single target therapy has been paid attention to by researchers. Combined therapies, or multitargeted therapies have been described in various reports (Dizaji et al, 2012;Hossain et al, 2012;Wang et al, 2013;Yelskaya et al, 2013;Yuan et al, 2013). Combined therapies improve therapeutic efficacy probably through synergistic, complementary effects or new signaling pathways (Dizaji et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

CRM197 in Combination With shRNA Interference of VCAM-1 Displays Enhanced Inhibitory Effects on Human Glioblastoma Cells

Lin

Wang

et al. 2015

J. Cell. Physiol.

View full text Add to dashboard Cite

CRM197 is a naturally nontoxic diphtheria toxin mutant that binds and inhibits heparin-binding epidermal growth factor-like growth factor. CRM197 serves as carrier protein for vaccine and other therapeutic agents. CRM197 also inhibits the growth, migration, invasion and induces apoptosis in various tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we aimed to investigate the role and mechanism of CRM197 combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioblastoma cells. U87 and U251 human glioblastoma cells were treated with CRM197 (10 μg/ml) and shRNA interfering technology was employed to silence VCAM-1 expression. Cell viability, migration, invasiveness and apoptosis were assessed with CCK8, Transwell and Annexin V-PE/7-AAD staining. Activation of cleaved caspase-3, 8 and 9, activity of matrix metalloproteinase-2/9 (MMP-2/9) and expression of phosphorylated Akt (p-Akt) were also checked. Results showed that CRM197 and shRNA-VCAM-1 not only significantly inhibited the cell proliferation, migration, invasion, but also promoted the apoptosis of U87 and

show abstract

Synergistic Inhibition of Survival, Proliferation, and Migration of U87 Cells with a Combination of LY341495 and Iressa

Cited by 33 publications

References 50 publications

Wnt3A Induces GSK‐3β Phosphorylation and β‐Catenin Accumulation Through RhoA/ROCK

Wnt3A Induces GSK‐3β Phosphorylation and β‐Catenin Accumulation Through RhoA/ROCK

Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic‐Induced Human Neuroblastoma SH‐SY5Y Cell Damage: The Impact of Cell Differentiation State

CRM197 in Combination With shRNA Interference of VCAM-1 Displays Enhanced Inhibitory Effects on Human Glioblastoma Cells

Contact Info

Product

Resources

About