Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
[PURPOSE] Dabrafenib, a molecular targeted drug, exhibits anti-tumor activities by inhibiting BRAF in a MAPK signaling pathway, but provides adverse effects such as dry skin. As dry skin is associated with abnormal sebaceous gland functions, it is speculated that dabrafenib influences sebaceous lipogenesis. In this study, we examined whether dabrafenib regulates sebum production in hamster sebocytes (HamSEB). [METHODS] Sebum production and accumulation were analyzed by Nile red and Oil red O staining, respectively. The level of ERK phosphorylation was measured by Western blotting. [RESULTS] Dabrafenib suppressed sebum production and accumulation, which were augmented by insulin and 5α-dihydrotestosterone (DHT) in HamSEB. Dabrafenib was found to promote ERK phosphorylation, and the ERK phosphorylation was enhanced in the presence of insulin and DHT. In addition, a MEK inhibitor, trametinib was found to abolish the dabrafenib-suppressed sebum production and accumulation in both insulin and DHT-treated HamSEB. [DISCUSSION] Our findings suggest that dabrafenib suppresses sebum production and accumulation by an increase of ERK phosphorylation in HamSEB. Thus, the dabrafenib-mediated activation of ERK pathway in sebaceous glands is associated with the onset of dry skin as its adverse effect in the skin.
