Repurposing of sildenafil as antitumour; induction of cyclic guanosine monophosphate/protein kinase G pathway, caspase-dependent apoptosis and pivotal reduction of Nuclear factor kappa light chain enhancer of activated B cells in lung cancer.
J Pharm Pharmacol
; 73(8): 1080-1091, 2021 Jul 07.
Article
em En
| MEDLINE
| ID: mdl-33856030
ABSTRACT
OBJECTIVES:
Lung cancer is one of the most frequent types of cancers that lead to death. Sildenafil is a potent inhibitor of phosphodiesterase-5 and showed potential anticancer effects, which has not yet been fully evaluated. Thus, this study aims to investigate the potential anticancer effect of sildenafil in urethane-induced lung cancer in BALB/c mice.METHODS:
Five-week-old male BALB/c mice were treated with either (i) normal saline only, (ii) sildenafil only 50 mg kg-1/ P.O every other day for the last four successive weeks, (iii) urethane 1.5 gm kg-1 i.p (at day 1 and day 60), (iv) carboplatin after urethane induction, or (v) sildenafil after urethane induction. KEYFINDINGS:
It was shown that sildenafil significantly increased the levels of cGMP and Caspase-3 with a reduction of NF-κB, Bcl-2, Cyclin D1, intercellular adhesion molecule 1, matrix metalloproteinase-2 levels and normalisation of Nrf2 along with pronounced improvement in the histological patterns.CONCLUSIONS:
These results indicated that sildenafil markedly induces cell cycle arrest, apoptosis and inhibits the metastatic activity through activation of cyclic guanosine monophosphate/protein kinase G pathway and down-regulation of cyclin D1 and nuclear factor kappa light chain enhancer of activated B cells with downstream anti-apoptotic gene Bcl-2, which underscores the critical importance of future using sildenafil in the treatment of lung cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Pulmao
Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Proteínas Quinases Dependentes de GMP Cíclico
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GMP Cíclico
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Citrato de Sildenafila
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Neoplasias Pulmonares
Limite:
Animals
Idioma:
En
Revista:
J Pharm Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Egito