Integrating computational and experimental chemical biology revealed variable anticancer activities of phosphodiesterase isoenzyme 5 inhibitors (PDE5i) in lung cancer
Abstract
Phosphodiesterase 5 (PDE5), an enzyme responsible for catalyzing the degradation of cyclic guanosine monophosphate (cGMP), has been linked to the development of cancer. PDE5 inhibitors (PDE5i), such as sildenafil (Viagra) and tadalafil (Cialis), work by blocking the action of PDE5 and are used primarily as treatments for erectile dysfunction and arterial hypertension. Some studies suggested a potential link between PDE5i and increased cancer risk, while other studies showed preferable antitumor effects. The present study is attempting to shed light on the systems biology effects of PDE5i by applying an integrative informatics approach followed by experimental validation methods including cell viability, cell motility, and proliferation capacity. Cell cycle and apoptosis analyses were carried out using flow cytometry, while real-time polymerase chain reaction (PCR) and western blotting were used to determine the relative gene and protein expression respectively. Our results indicated that the examined PDE5i significantly inhibited the proliferation of lung cancer cells, in addition to reducing wound closure and the mean colony count and size. Furthermore, PDE5i increased the early and late apoptotic activities and suppressed the gene and protein expression of PDE5 in lung cancer cells. The combination of cisplatin and raloxifene with PDE5i resulted in a synergistic effect. This study provides solid evidence supporting the anti-tumorigenic effect of PDE5i in lung cancer cells.
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