Repurposing phosphodiesterase-5 inhibitors as chemoadjuvants
Abstract
Phosphodiesterase-5 (PDE5) inhibitors have shown a beneficial effect in a variety of clinical conditions, such as benign prostate hyperplasia, pulmonary arterial hypertension, female sexual arousal disorder, overactive bladder, and incontinence, Raynaud's disease, heart failure and stroke among others (Sandner et al., 2007). Three PDE5 inhibitors, sildenafil (Viagra™), tadalafil (Cialis™) and vardenafil (Levitra™) are clinically approved and are widely used for the treatment of erectile dysfunction. A retrospective analysis determined that men treated with PDE5 for ED had less chance of having prostate cancer. This population of men had significantly lower documented diagnosis of elevated prostate-specific antigen and higher percentage of benign prostatic hyperplasia compared to men not treated with PDE-5 inhibitors (Chavez et al., 2013). Emerging evidence indicates that PDE5 inhibitors are multi-targeting agents and have promising results in the treatment of variety of tumors. Here we propose the possibility of repurposing of PDE5 inhibitors for adjuvant chemotherapy.
PDE5 contributes to the regulation of intracellular cyclic GMP (cGMP) pools (see Figure Figure1)1) that have been shown to be decreased along with protein kinase-G (PKG), a downstream effector of cGMP, in variety of different tumors such as breast cancer, colon cancer and human oral squamous cell carcinoma (hOSCC) (Spoto et al., 2003; Zhu and Strada, 2007; Di et al., 2010). PDE5 hydrolyzes the 3′,…
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