Tyrosine phosphatase inhibitors combined with retinoic acid can enhance differentiation of neuroblastoma cells and trigger ERK- and AKT-dependent, p53-independent senescence

Clark, Owen; Daga, Shruti; Stoker, Andrew W.

doi:10.1016/j.canlet.2012.09.014

Cited by 33 publications

(39 citation statements)

References 58 publications

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“…4A). We have seen related, strong AKT activation in our studies of combination BMOV/retinoic acid treatment on neuroblastoma cells [17]. In that study, hyperactivation of AKT was necessary in part for driving senescence in SKNSH and SK-SY5Y cells.…”

Section: Bmov/bso Stimulation Of Akt Is Not Necessary For Cytotoxicitymentioning

confidence: 54%

“…Oxovanadium compounds, in combination with retinoic acid, induce differentiation and senescence in SKNSH, SH-SY5Y and LAN-5 [17]. We found that VA did not significantly increase apoptosis (as judged by sub-G1 content) in SKNSH, SH-SY5Y, or several unrelated cell lines (Fig.…”

Section: Bmov Induces Cytotoxicity In Neuroblastoma Cellsmentioning

confidence: 57%

“…S1). SKNAS and SKNDZ are resistant to BMOV-induced differentiation [17], and also cytotoxicity with 10 μM BMOV (Fig. 1C).…”

Section: Bmov Induces Cytotoxicity In Neuroblastoma Cellsmentioning

confidence: 88%

“…S6). Interestingly, SKNSH and SH-SY5Y, which differentiate in response to BMOV [17], are relatively resistant to this chemical combination ( Supplementary Fig. S6).…”

Section: Bmov Cytotoxicity Is Enhanced By Depletion Of Cellular Glutamentioning

confidence: 99%

“…Our own studies on neuroblastoma cells have demonstrated that oxovanadium compounds, which are broad inhibitors of PTP enzymes [16], induce differentiation and senescence in specific neuroblastoma cell lines [17]. Oxovanadium-based chemicals have long been of interest in cancer biology, with several studies demonstrating their anti-proliferative and anti-survival properties in tumour-derived cell lines [18].…”

Section: Introductionmentioning

confidence: 99%

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Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine

Clark¹,

Park²,

Florio³

et al. 2015

Cancer Letters

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In a wide range of neuroblastoma-derived lines oxovanadium compounds such as bis(maltolato)oxovanadium(IV) (BMOV) are cytotoxic. This is not explained by oxidative stress or inhibition of ion channels. Genotoxicity is unlikely given that a p53 response is absent and p53-mutant lines are also sensitive. Cytotoxicity is inhibited by N-acetyl cysteine and glutathione ester, indicating that BMOV action is sensitive to cytoplasmic redox and thiol status. Significantly, combining BMOV with glutathione synthesis inhibition greatly enhances BMOV-induced cell death. This combination treatment triggers high AKT pathway activation, highlighting the potential functional importance of PTP inhibition by BMOV. AKT activation itself, however, is not required for cytotoxicity. Oxovanadium compounds may thus represent novel leads as p53-independent therapeutics for neuroblastoma.

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Section: Bmov/bso Stimulation Of Akt Is Not Necessary For Cytotoxicitymentioning

confidence: 54%

Section: Bmov Induces Cytotoxicity In Neuroblastoma Cellsmentioning

confidence: 57%

“…S1). SKNAS and SKNDZ are resistant to BMOV-induced differentiation [17], and also cytotoxicity with 10 μM BMOV (Fig. 1C).…”

Section: Bmov Induces Cytotoxicity In Neuroblastoma Cellsmentioning

confidence: 88%

“…S6). Interestingly, SKNSH and SH-SY5Y, which differentiate in response to BMOV [17], are relatively resistant to this chemical combination ( Supplementary Fig. S6).…”

Section: Bmov Cytotoxicity Is Enhanced By Depletion Of Cellular Glutamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine

Clark¹,

Park²,

Florio³

et al. 2015

Cancer Letters

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Meeting report-3rd Neuroblastoma Research Symposium, Liverpool, 6-7th November, 2013

Bell

Chen

Viprey

et al. 2014

Pediatr Blood Cancer

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Neuroblastoma is an embryonal malignancy of the developing neural crest. Despite improvements in treatment, prognoses remain dire for patients with high-risk disease. Interest in this enigmatic cancer has led to a rapidly changing research landscape and we report on the recent advances in four themes that were discussed at the 3rd Neuroblastoma Research Symposium: (1) The epigenetic signature of neuroblastoma and the epigenetic control of tumour development, (2) novel approaches to targeting MYCN, (3) valuable in vivo modelling and (4) improving differentiation therapies based on a knowledge of normal sympathetic neuron development. Through lively discussion, the development of combined therapies with synergistic effects for which we have a good mechanistic understanding emerged as offering greatest promise. Drug synergies enhance efficacy but also specificity, the latter crucial for reducing long-term side effects in young children.

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UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts

et al. 2018

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Tyrosine phosphatase inhibitors combined with retinoic acid can enhance differentiation of neuroblastoma cells and trigger ERK- and AKT-dependent, p53-independent senescence

Cited by 33 publications

References 58 publications

Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine

Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine

Meeting report-3rd Neuroblastoma Research Symposium, Liverpool, 6-7th November, 2013

UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts

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