Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity

Autor(en): Melnik, Bodo C.
Stichwörter: 13-CIS RETINOIC ACID; 13-CIS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; adverse effects; apoptosis; BIPOLAR DISORDER; Dermatology; FoxOs; GENE-EXPRESSION; GROWTH-FACTOR-I; INCREASED EXPRESSION; INFLAMMATORY-BOWEL-DISEASE; isotretinoin; ORAL ISOTRETINOIN; PROGRAMMED CELL-DEATH; TRAIL
Erscheinungsdatum: 2017
Herausgeber: ACTA DERMATO-VENEREOLOGICA
Journal: ACTA DERMATO-VENEREOLOGICA
Volumen: 97
Ausgabe: 2
Startseite: 173
Seitenende: 181
Zusammenfassung: 
Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. 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. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoininduced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.
ISSN: 00015555
DOI: 10.2340/00015555-2535

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