Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells

Mayevska, O. M.; Chen, Oleg; Karatsai, Olena; Bobak, Yaroslav; Barska, Maryna; Lyniv, L. S.; Pavlyk, Iuliia; Rzhepetskyy, Yuriy; Igumentseva, N. I.; Redowicz, Maria Jolanta; Stasyk, Oleh

doi:10.1016/j.yexcr.2017.04.003

Cited by 6 publications

(4 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell migration and invasion play a key role in cancer metastasis [ 44 ]. We previously demonstrated that arginine deficiency specifically impaired the motility and adhesive interactions of human glioblastoma and melanoma cells [ 25 , 45 ]. The above-described exacerbated alterations of cell morphology observed under canavanine co-treatment could be associated with changes in cell adhesion and motility.…”

Section: Resultsmentioning

confidence: 99%

“…It is known that tumor invasiveness and aggressiveness are highly dependent on malignant cell motility. A negative impact of arginine deprivation as a monotreatment on the motility of glioblastoma, melanoma and colon carcinoma cells was observed [ 25 , 45 , 70 ]. This phenomenon in glioblastoma cells was most probably evoked by the decrease in the content of the positively charged arginylated form of β-actin and polymerized F-actin [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Combinatory Treatment of Canavanine and Arginine Deprivation Efficiently Targets Human Glioblastoma Cells via Pleiotropic Mechanisms

Karatsai

Shliaha

Jensen

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

Glioblastomas are the most frequent and aggressive form of primary brain tumors with no efficient cure. However, they often exhibit specific metabolic shifts that include deficiency in the biosynthesis of and dependence on certain exogenous amino acids. Here, we evaluated, in vitro, a novel combinatory antiglioblastoma approach based on arginine deprivation and canavanine, an arginine analogue of plant origin, using two human glioblastoma cell models, U251MG and U87MG. The combinatory treatment profoundly affected cell viability, morphology, motility and adhesion, destabilizing the cytoskeleton and mitochondrial network, and induced apoptotic cell death. Importantly, the effects were selective toward glioblastoma cells, as they were not pronounced for primary rat glial cells. At the molecular level, canavanine inhibited prosurvival kinases such as FAK, Akt and AMPK. Its effects on protein synthesis and stress response pathways were more complex and dependent on exposure time. We directly observed canavanine incorporation into nascent proteins by using quantitative proteomics. Although canavanine in the absence of arginine readily incorporated into polypeptides, no motif preference for such incorporation was observed. Our findings provide a strong rationale for further developing the proposed modality based on canavanine and arginine deprivation as a potential antiglioblastoma metabolic therapy independent of the blood–brain barrier.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combinatory Treatment of Canavanine and Arginine Deprivation Efficiently Targets Human Glioblastoma Cells via Pleiotropic Mechanisms

Karatsai

Shliaha

Jensen

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rationally designed combination modalities based on Arg deprivation may overcome these drawbacks to some extent. We proposed and evaluated several combination approaches including the autophagy inhibitor chloroquine, the arginine proteomimetic toxic analogue Cav, and exogenous donor of nitric oxide as well as their triple combinations, which shall now be further tested in animal models (Vynnytska et al, 2011; Shuvayeva et al, 2014; Kurlishchuk et al, 2016; Mayevska et al, 2017). Other groups elaborated several similar or alternative approaches (Alexandrou et al, 2018; Harding et al, 2018; Hinrichs et al, 2018; Przystal et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Indospicine combined with arginine deprivation triggers cancer cell death via caspase‐dependent apoptosis

Shuvayeva

Bobak

Vovk

et al. 2020

Cell Biology International

View full text Add to dashboard Cite

Arginine‐deprivation therapy is a rapidly developing metabolic anticancer approach. To overcome the resistance of some cancer cells to this monotherapy, rationally designed combination modalities are needed. In this report, we evaluated for the first time indospicine, an arginine analogue of Indigofera plant genus origin, as potential enhancer compound for the metabolic therapy that utilizes recombinant human arginase I. We demonstrate that indospicine at low micromolar concentrations is selectively toxic for human colorectal cancer cells only in the absence of arginine. In arginine‐deprived cancer cells indospicine deregulates some prosurvival pathways (PI3K‐Akt and MAPK) and activates mammalian target of rapamycin, exacerbates endoplasmic reticulum stress and triggers caspase‐dependent apoptosis, which is reversed by the exposure to translation inhibitors. Simultaneously, indospicine is not degraded by recombinant human arginase I and does not inhibit this arginine‐degrading enzyme at its effective dose. The obtained results emphasize the potential of arginine structural analogues as efficient components for combinatorial metabolic targeting of malignant cells.

show abstract

“…However, because of the gaseous state and short half-life in the body, it is difficult to use NO as a therapeutic agent directly. To solve this problem, a series of NO donors have been designed, such as N -diazeniumdiolates (NONOates), sodium nitroprusside (SNP), S-nitrosothiols (RSNOs), and nitric oxide-donor doxorubicins (NO–DOXOs). ,− Unfortunately, these low molecular weight compounds lack specificity and are easily cleared during blood circulation. In order to realize tumor targeting NO delivery and prolong its life in vivo, NO-generating nanoparticles that can release NO by some exogenous stimulating factors such as X-ray, ultraviolet and near-infrared (NIR) light have been constructed.…”

Section: Introductionmentioning

confidence: 99%

Intracellular NO-Generator Based on Enzyme Trigger for Localized Tumor-Cytoplasm Rapid Drug Release and Synergetic Cancer Therapy

Hou

Zhang

Yang

et al. 2018

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Nitric oxide (NO) is an important biological messenger implicated in tumor therapy. However, current NO release systems suffer from some disadvantages, such as hydrolysis during blood circulation, poor specificity, and robust irradiation for stimuli. Accordingly, we constructed an intracellular enzyme-triggered NO-generator to achieve tumor cytoplasm-specific disruption and localized rapid drug release. Diethylamine NONOate (DEA/NO) was used as a NO donor and conjugated with hyaluronic acid (HA) to form self-assembly micelle (HA-DNB-DEA/NO), and encapsulate chemotherapeutic agent (doxorubicin (DOX)) into its hydrophobic core (DOX@HA-DNB-DEA/NO). After HA receptor mediated internalization into tumor cells, HA shell would undergo digestion into small conjugated pieces by hyaluronidase. Meanwhile, DOX@HA-DNB-DEA/NO also responded to the intratumoral overexpressed glutathion and glutathione S-transferase π, leading to the intracellular NO production and controlled DOX rapid release. In vitro and in vivo results proved the enzyme-dependent and enhanced targeting delivery profile, and demonstrated that NO and DOX could colocate in specific tumor site, which provided a precondition for exerting their synergistic efficacy. Moreover, expression of p53 protein was upregulated in tumor tissue after treatment, indicating that NO induced cell apoptosis mediated by tumor suppressor gene p53. Overall, this intelligent drug loaded NO-generator might perform as an enhancer to realize better clinical outcomes.

show abstract

Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells

Cited by 6 publications

References 41 publications

Combinatory Treatment of Canavanine and Arginine Deprivation Efficiently Targets Human Glioblastoma Cells via Pleiotropic Mechanisms

Combinatory Treatment of Canavanine and Arginine Deprivation Efficiently Targets Human Glioblastoma Cells via Pleiotropic Mechanisms

Indospicine combined with arginine deprivation triggers cancer cell death via caspase‐dependent apoptosis

Intracellular NO-Generator Based on Enzyme Trigger for Localized Tumor-Cytoplasm Rapid Drug Release and Synergetic Cancer Therapy

Contact Info

Product

Resources

About