Effect of oral isotretinoin on the nucleo-cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

Oral isotretinoin is the most effective anti-acne drug with the strongest sebum-suppressive effect caused by sebocyte apoptosis. It has been hypothesized that upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin-induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the distribution of the pro-apoptotic transcription factors FoxO1 and FoxO3 in the nuclear and cytoplasmic compartments of human sebocytes in vivo before and during isotretinoin treatment of acne patients. Immunohistochemical analysis of skin biopsies with antibodies distinguishing phosphorylated and non-phosphorylated human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six weeks after initiation of isotretinoin therapy, and in acne-free control patients not treated with isotretinoin. Our in vivo study demonstrates a significant increase in the nucleo-cytoplasmic ratio of non-phosphorylated FoxO1 and FoxO3 during isotretinoin treatment of acne patients. Translational and presented experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3 proteins is involved in isotretinoin-induced pro-apoptotic signalling in sebocytes confirming the scientific hypothesis of isotretinoin-mediated upregulation of FoxO expression.