Active substances: Isotretinoin
Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin.
This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis.
Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.
E-mail: melnik t-online. Isotretinoin was introduced to the market by Hoffman-La Roche in 1982.
However, treatment with isotretinoin is associated with adverse effects, the most serious of which is teratogenicity 2. Further manageable adverse effects are mucocutaneous side-effects, increases in transaminases, and hypertriglyceridaemia.
Rare adverse effects are depression and inflammatory bowel disease.
The aim of this medical hypothesis is to show that the underlying common mechanism that explains the mode of action of isotretinoin and all its adverse effects is apoptosis.
The desired apoptotic effect of isotretinoin in the treatment of acne is discussed first, followed by its unwanted adverse effects, including teratogenicity.
Of all known anti-acne drugs, isotretinoin exhibits the strongest sebum-suppressive effect 7. This sebum-suppressive activity is primarily based on sebocyte apoptosis.
Nelson et al. In 2 further studies, Nelson et al. In patients with acne, FoxO activity is suppressed due to enhanced growth factor signalling 15—17.
In sebocytes, the prodrug isotretinoin 13-cis retinoic acid is isomerized to all-trans retinoic acid ATRA Fig. FoxO 3 a is a key transcription factor of apoptosis 25.