Original ArticlesSurvival mechanisms induced by 12-O-tetradecanoylphorbol-13-acetate in normal human melanocytes include inhibition of apoptosis and increased Bcl-2 expressionArita, Y.; Santiago-Schwarz, F.; Coppock, D. L.*Author Information Oncology Research Laboratory, Division of Oncology (Y. Arita, D. L. Coppock) and Cellular Immunology Research Laboratory, Division of Rheumatology and Allergy (F. Santiago-Schwarz), Winthrop University Hospital, 222 Station Plaza North, #300C Mineola, New York 11501, USA. Department of Medicine, SUNY Stony Brook Medical Center, Stony Brook, New York 11790, USA. Tel: (+1) 516 663 4616; Fax: (+1) 516 663 4614; Email: [email protected] (F. Santiago-Schwarz, D. L. Coppock). *To whom correspondence should be addressed Received 24 January 2000; accepted in revised form 19 June 2000 Melanoma Research: October 2000 - Volume 10 - Issue 5 - p 412-420 Buy Abstract Phorbol esters, which activate protein kinase C, stimulate the growth of normal human melanocytes yet inhibit the growth of most melanoma cells. We investigated whether apoptosis mediates the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on melanocyte and melanoma cell growth. Few apoptotic cells were present when melanocytes were cultured with TPA. Upon removal of TPA, the number of apoptotic cells increased over 10 days. Addition of TPA did not induce apoptosis in a metastatic melanoma cell line, Demel, although it strongly inhibited its growth. Protection of normal melanocytes from apoptosis was associated with high levels of Bcl-2. Following withdrawal of TPA from melanocytes, the expression of Bcl-2 decreased steadily. Bax and Bcl-XL levels did not differ between melanoma cells or melanocytes and were unaffected by the addition of TPA. These results suggest that TPA plays an important role in stimulating the growth of melanocytes by promoting anti-apoptotic mechanisms associated with high levels of Bcl-2. © 2000 Lippincott Williams & Wilkins, Inc.