The reputation of Viagra is getting better! The Joy of Sex! đ
"... found that sildenafil, Viagra’s active ingredient, may restrict cancer metastasis through a newly discovered biological mechanism. ...
showed that sildenafil limits cancer cells’ ability to make use of cholesterol, an essential component of cellular membranes. Cholesterol is particularly important for cancer cells seeking to break away from the primary tumor, migrate throughout the body and invade distant organs. When their access to cholesterol is disrupted, these cells have a harder time forming metastases.
Sildenafil creates this disruption by blocking an enzyme called phosphodiesterase type 5, or PDE5, thereby increasing the levels of a signaling molecule known as cGMP.
Elevated cGMP levels dilate blood vessels, increasing blood flow to the penis – the effect that has made Viagra a successful treatment for erectile dysfunction.
But ... discovered that cGMP also binds to a protein responsible for transporting cholesterol within cells. As a result, less cholesterol is available for the cell’s needs, and cancer cells, it turns out, are particularly vulnerable to this reduction in cholesterol supply. ..."
From the abstract:
"Non-canonical metabolic functions of signaling molecules contribute to cancer plasticity and metastatic progression. Here, we demonstrated that PDE5a inhibitors, including sildenafil (Viagra), induced lysosomal cholesterol accumulation across multiple mouse and human cancer models, reducing cholesterol bioavailability and impairing cancer cell migration and metastasis. Cancer cells exhibited heightened sensitivity due to reduced lysosomal gene expression, rendering them particularly vulnerable to disrupted cholesterol trafficking.
Mechanistically, elevated cGMP bound the lysosomal cholesterol transporter NPC1, impairing cholesterol export and phenocopying Niemann–Pick type C pathology. The resulting cholesterol depletion disrupted membrane lipid rafts and mitochondrial bioenergetics, thereby limiting metastatic capacity and triggering compensatory SREBP2 activation with increased cholesterol synthesis.
Combining sildenafil with statins yields additive antimetastatic effects by concurrently blocking lysosomal cholesterol export and cholesterol biosynthesis. Consistently, analysis of digital health records demonstrated significantly improved survival among sildenafil users, with a dose-dependent additive benefit observed when combined with statins.
Together, these findings identify increasing cGMP levels through PDE5a inhibition as a potential strategy to restrict metastasis and offer a potential mechanistic basis for the beneficial effects of sildenafil."
Breast cancer tissue after treatment with sildenafil. Cholesterol (green) is trapped within tiny sac-like organelles called lysosomes, making it unavailable to the cancer cells. Cell nuclei are shown in purple
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