Betulinic acid induces apoptosis in skin cancer cells and differentiation in normal human keratinocytes

• Published in: Experimental dermatology Vol. 14; no. 10; pp. 736 - 743
• Main Authors: Galgon, Tino, Wohlrab, Wolfgang, Dräger, Birgit
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Munksgaard International Publishers 01.10.2005; Blackwell
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; apoptosis; Apoptosis - drug effects; betulinic acid; Biological and medical sciences; Cell Differentiation - drug effects; Cell Line; Cell Line, Tumor; Cell Survival - drug effects; Dermatology; differentiation; Dose-Response Relationship, Drug; Humans; keratinocyte; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - physiology; Medical sciences; melanocyte; Melanoma - pathology; Necrosis; Skin Neoplasms - pathology; Triterpenes - pharmacology; Human; Cell culture; Skin disease; differentiation; Dermatology; Melanocyte; betulinic acid; Skin cancer; Cell death; Plant origin; Keratinocyte; Tumor cell; Apoptosis
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2005.00352.x

:  Betulinic acid (BA), a pentacyclic triterpene of plant origin, induces cell death in melanoma cells and other malignant cells of neuroectodermal origin. Little is known about additional biological effects in normal target cells. We show, in this study, that BA induces differentiation as well as cell death in normal human keratinocytes (NHK). Cytotoxicity profiles of BA are compared among normal human keratinocytes, HaCaT cells, IGR1 melanoma cells and normal melanocytes. As expected, BA is toxic to all cell types, normal and malignant, but varies in its cytotoxic potency and in the extent of induction of apoptotic vs. necrotic cell death in the four different skin cell types. Apoptosis is proved by annexin V and Apo2.7 binding and by DNA fragmentation. Induction of differentiation‐associated antigens in keratinocytes – filaggrin and involucrin – is demonstrated, together with specific morphological changes in treated cell cultures. BA, apart from its cytotoxic activities in cellular systems, is capable of inducing differentiation of NHK into corneocytes without immediately provoking apoptotic cell death.