Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis

Area of Science:

• Dermatology
• Oncology
• Pharmacology

Background:

• Ultraviolet (UV) radiation is a known carcinogen causing skin cancer.
• The beta-blocker carvedilol has previously shown inhibitory effects on epidermal cell transformation and skin hyperplasia.
• Carvedilol possesses UV-absorbing properties, necessitating a control to distinguish pharmacological effects from sunscreen effects.

Purpose of the Study:

• To investigate the potential of carvedilol in preventing UV-induced carcinogenesis.
• To differentiate the chemopreventive effects of carvedilol from its UV-absorbing properties.
• To evaluate carvedilol's efficacy in reducing UV-induced skin inflammation and tumor development.

Main Methods:

• JB6 P+ cells were used to assess carvedilol's effect on UV-induced neoplastic transformation.
• 4-hydroxycarbazole (4-OHC) served as a control for UV absorption.
• Mouse models were employed to evaluate carvedilol's impact on UV-induced skin inflammation, DNA damage, and carcinogenesis.

Main Results:

• Both carvedilol and 4-OHC inhibited chronic UV-induced transformation in JB6 P+ cells.
• Carvedilol, but not 4-OHC, inhibited EGF-mediated transformation and reduced UV-induced AP-1 and NF-κB activity.
• Topical carvedilol reduced UV-induced skin hyperplasia, DNA damage, and inflammatory markers (IL1β, IL6, COX-2) in mice.
• In a chronic UV exposure mouse model, carvedilol increased tumor latency and decreased tumor incidence and multiplicity.

Conclusions:

• Carvedilol demonstrates novel chemopreventive activity against UV-induced skin carcinogenesis.
• The anti-carcinogenic effects of carvedilol are likely due to its pharmacological properties, not solely UV absorption.
• Topical carvedilol may be a potential therapeutic agent for preventing UV-induced skin inflammation and cancer.