Protein kinase inhibitor-based cancer therapies: Considering the potential of nitric oxide (NO) to improve cancer treatment

Ghione, S; Mabrouk, Nesrine; Paul, Catherine; Bettaı̈eb, Ali; Plenchette, Stéphanie

doi:10.1016/j.bcp.2020.113855

Cited by 13 publications

(11 citation statements)

References 170 publications

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“…Only in recent years the combination of NOPD with conventional chemotherapeutics has been reported [ 34 , 35 , 36 , 37 ], highlighting the double role of photo-released NO as a cytotoxic agent [ 34 ] and inhibitor of the cellular efflux pumps [ 35 , 36 ]. Recently, the potential role of NO in combination with protein kinase inhibitors has been proposed, opening new prospects for improving cancer treatments with this class of drugs [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Anticancer Activity of Sorafenib through Its Combination with a Nitric Oxide Photodelivering β-Cyclodextrin Polymer

et al. 2022

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In this contribution, we report a strategy to enhance the therapeutic action of the chemotherapeutic Sorafenib (SRB) through its combination with a multifunctional β-cyclodextrin-based polymer able to deliver nitric oxide (NO) and emit green fluorescence upon visible light excitation (PolyCDNO). The basically water-insoluble SRB is effectively encapsulated in the polymeric host (1 mg mL−1) up to a concentration of 18 μg mL−1. The resulting host-guest supramolecular complex is able to release SRB in sink conditions and to preserve very well the photophysical and photochemical properties of the free PolyCDNO, as demonstrated by the similar values of the NO release and fluorescence emission quantum efficiencies found. The complex PolyCDNO/SRB internalizes in HEP-G2 hepatocarcinoma, MCF-7 breast cancer and ACHN kidney adenocarcinoma cells, localizing in all cases mainly at the cytoplasmic level. Biological experiments have been performed at SRB concentrations below the IC50 and with light doses producing NO at nontoxic concentrations. The results demonstrate exceptional mortality levels for PolyCDNO/SRB upon visible light irradiation in all the different cell lines tested, indicating a clear synergistic action between the chemotherapeutic drug and the NO. These findings can open up exciting avenues to potentiate the anticancer action of SRB and, in principle, to reduce its side effects through its use at low dosages when in combination with the photo-regulated release of NO.

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Section: Introductionmentioning

confidence: 99%

Enhancing the Anticancer Activity of Sorafenib through Its Combination with a Nitric Oxide Photodelivering β-Cyclodextrin Polymer

et al. 2022

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“…CDK mainly affects the cell cycle, MAPK is related to cell division, and GSK3 family is related to glycogen synthesis 8 . These pathways have effects on cell proliferation and active division, and are one of the main development directions of new PKI drugs 251 . Table 1 briefly summarized the protein kinase group, family, target, disease, and years approved by FDA in recent 5 years.…”

Section: Discussionmentioning

confidence: 99%

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

Pang

Wang

Qin

et al. 2022

MedComm

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Protein phosphorylation is an important post‐transcriptional modification involving an extremely wide range of intracellular signaling transduction pathways, making it an important therapeutic target for disease intervention. At present, numerous drugs targeting protein phosphorylation have been developed for the treatment of various diseases including malignant tumors, neurological diseases, infectious diseases, and immune diseases. In this review article, we analyzed 303 small‐molecule protein phosphorylation kinase inhibitors (PKIs) registered and participated in clinical research obtained in a database named Protein Kinase Inhibitor Database (PKIDB), including 68 drugs approved by the Food and Drug Administration of the United States. Based on previous classifications of kinases, we divided these human protein phosphorylation kinases into eight groups and nearly 50 families, and delineated their main regulatory pathways, upstream and downstream targets. These groups include: protein kinase A, G, and C (AGC) and receptor guanylate cyclase (RGC) group, calmodulin‐dependent protein kinase (CaMK) group, CMGC [Cyclin‐dependent kinases (CDKs), Mitogen‐activated protein kinases (MAPKs), Glycogen synthase kinases (GSKs), and C dc2‐like kinases (CLKs)] group, sterile (STE)‐MAPKs group, tyrosine kinases (TK) group, tyrosine kinase‐like (TKL) group, atypical group, and other groups. Different groups and families of inhibitors stimulate or inhibit others, forming an intricate molecular signaling regulatory network. This review takes newly developed new PKIs as breakthrough point, aiming to clarify the regulatory network and relationship of each pathway, as well as their roles in disease intervention, and provide a direction for future drug development.

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“…Nitrosothiols are compounds generated by the combination of NO and thiols and possess antioxidation properties and extend the duration of NO’s effect. In the environment of the human body they engage in several vital physiological processes . Nitrosothiols may be degraded catalytically to create NO under specified specific circumstances, such as pH, light, temperature which can drive-break the S-NO link in R-SNO compounds to break and release NO.…”

Section: Small Molecular Weight No Donorsmentioning

confidence: 99%

Nitric Oxide and Tumors: From Small-Molecule Donor to Combination Therapy

Huang

Zhang

Luo

et al. 2022

ACS Biomater. Sci. Eng.

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As an important endogenous signaling molecule, nitric oxide (NO) is involved in various physiological and pathological activities in living organisms. It is proved that NO plays a critical role in tumor therapy, while the extremely short half-life and nonspecific distribution of NO greatly limit its further clinical applications. Thus, the past few decades have witnessed the progress made in conquering these shortcomings, including developing innovative NO donors, especially smart and multimodal nanoplatforms. These platforms can precisely control the spatiotemporal distribution of therapeutic agents in the organism, which make big differences in tumor treatment. Here current NO therapeutic mechanisms for cancer, NO donors from small molecules to smart-responsive nanodrug delivery platforms, and NObased combination therapy are comprehensively reviewed, emphasizing outstanding breakthroughs in these fields and hoping to bring new insights into NO-based tumor treatments.

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Protein kinase inhibitor-based cancer therapies: Considering the potential of nitric oxide (NO) to improve cancer treatment

Cited by 13 publications

References 170 publications

Enhancing the Anticancer Activity of Sorafenib through Its Combination with a Nitric Oxide Photodelivering β-Cyclodextrin Polymer

Enhancing the Anticancer Activity of Sorafenib through Its Combination with a Nitric Oxide Photodelivering β-Cyclodextrin Polymer

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

Nitric Oxide and Tumors: From Small-Molecule Donor to Combination Therapy

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