Effect of a new retinoid, arotinoid (Ro 13-6298), on in vitro keratinocyte proliferation and differentiation

Abstract

In preliminary clinical trials, a new retinoid, Arotinoid Ro 13-6298, was found highly effective in hyperproliferation and keratotic disorders. The aim of this investigation was to study the effect of Arotinoid on in vitro neonatal mouse keratinocyte proliferation and differentiation. Five doses of Arotinoid were tested. [3H]-Tdr labeling techniques and autoradiography were used to quantitate proliferation. Differentiation was assessed using one-dimensional polyacrylamide gel electrophoresis and autoradiography of six specific protein fractions extracted from the cells using a series of buffers. Our results indicate that Arotinoid is an extremely potent inhibitor of keratinocyte proliferation. Arotinoid significantly decreases the amount and synthesis of non-covalently and disulfide cross-linked keratins and cell envelopes while increasing the quantity of keratohyalin granule-associated proteins. No qualitative change in keratinocyte proteins was observed.