EFFECT OF BENZOYL PEROXIDE ON PROTEIN-KINASE-C IN CULTURED HUMAN EPIDERMAL-KERATINOCYTES

Benzoyl peroxide (BzPO) has been the most widely used topical agent fo r acne since the 1960s, This is true despite numerous reports that BzP O can enhance the development of carcinomas from murine epidermal papi llomas. Because activation of protein kinase C (PKC) is considered to to other epidermal tumor promoters, we wished to investigate the relat ionship between BzPO and PKC in cultured human epidermal keratinocytes (NHEK). We assayed (a) direct effects of BzPO on PKC activity in a ce ll-free system using semipurified human keratinocyte PKC, (b) BzPO eff ects on the subcellular distribution of PKC, and (c) BzPO modulation o f NHEK proliferation and phorbol ester-induced differentiation. NHEK m aintained in serum-free media (0.15 mM Ca2+) were treated with concent rations of BzPO in acetone from 100 nM to 500 mu M, with concentration s of acetone not exceeding 0.1%. No short-term translocation of PKC fr om cytosol to membrane was observed at any BzPO concentration. BzPO di d not downregulate subcellular levels of PKC activity after 24 h of ex posure. BzPO did not significantly antagonize phorbol ester-induced in hibition of proliferation or differentiation but did weakly antagonize Ca2+-induced differentiation. Consistent with a PKC-mediated mechanis m for Ca2+-induced differentiation, BzPO inhibited both human and muri ne PKC in a cell-free system. These results suggest that BzPO does not promote malignant conversion through a PKC-dependent mechanism, and i n fact, inhibits PKC activity in vitro.