Can Carvedilol Prevent Skin Cancer?

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It has recently been determined that α- and β-adrenergic receptors (α- and β-AR) as well as stress-related catecholamine hormones may have an impact on carcinogenesis. It is understood that the β-AR GRK/β-arrestin biased agonist carvedilol can induce β-AR-mediated transactivation of the EGFR.

Researchers wanted to determine if carvedilol, through activation of EGFR, can induce cancer. The researchers found that carvedilol did not lead to anchorage-independent growth of JB6 P+ cells, a model of skin cells used to study tumor growth.

At nontoxic concentration levels, though, a dose of carvedilol was shown to dependently inhibit EGF-inducedd malignant transformation of JB6 P+ cells, which leads researchers to believe that carvedilol is able to prevent cancer activity in skin cancer. The same was not observed in β-AR agonist isoproterenol and β-AR antagonist atenolol.

According to gene expression, receptor binding, and functional studies, only JB6 P+ cells can express β2-ARs. EGF-mediated activator protein-1 was inhibited by carvedilol but not atenolol. Researchers used a topical 7,12-dimethylbenz(α)anthracene (DMBA)-induced skin hyperplasia mice model to understand the in vivo cancer preventative activity of carvedilol.

The researchers found that oral and topical treatment with carvedilol inhibited DMBA-induced epidermal hyperplasia (P<0.05). They also found that topical and oral treatment with carvedilol reduced H-ras mutations, with topical treatment having the most potent effect.

It must be noted, however, that when a model included established cancer, carvedilol did not inhibit (or showed a very modest rate of inhibition) on tumor growth in lung cancer A549 cells in vitro and in vivo.

The researchers concluded that carvedilol may have the potential to be used as a chemoprevention agent against skin cancer and β-ARs may serve as a novel target for cancer prevention.

Biochemotherapy Shows Benefits in High-Risk Melanoma, But Newer Agents Will Get More Use
The β-blocker carvedilol may have the potential to be used as a chemoprevention agent against skin cancer.
The initial purpose of this study was to determine whether carvedilol, through activation of EGFR, can promote cancer. The results suggest that the cardiovascular drug carvedilol may be repurposed for skin cancer chemoprevention, but may not be an effective treatment of established tumors.

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