Abstract
The activation of the RAS-RAF-MEK-ERK signal pathway has been associated with tumor progression. A selective BRAF protein kinase inhibitor, vemurafenib, exhibits anti-tumorigenic activity in patients with metastatic melanoma. Many patients treated with vemurafenib develop common cutaneous disorders including dry skin and acne-like rashes, which are closely associated with the dysfunction of sebaceous glands and pilosebaceous units. However, there have been no reports to date that vemurafenib may modulate sebum production in sebaceous glands. In the present study, we examined whether or not vemurafenib directly influenced sebum production in hamster sebocytes (HamSEB) in vitro. Insulin-augmented intracellular lipid-droplet formation was enhanced by vemurafenib in HamSEB, which was due to the increased production of triacylglycerols (TG), a major component of sebum. On the other hand, vemurafenib was found to suppress 5α-dihydrotestosterone (5α-DHT)-induced lipid-droplet formation and TG production in HamSEB. Thus, vemurafenib is likely to enhance or suppress sebum production, depending on lipogenetic factor species in sebaceous glands. These findings may increase the clinical understanding of the side effects of vemurafenib.
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