Bryostatin 1 causes attenuation of TPA‑mediated tumor promotion in mouse skin.

Abstract

The present study was designed to investigate the tumor inhibitory potential of bryostatin 1 in a 12‑O‑tetradecanoylphorbol‑13‑acetate (TPA)‑induced mouse model of skin cancer. The radical inhibition potential of various doses of bryostatin 1 was investigated against 2,2‑diphenyl‑1‑picrylhydrazyl (DPPH) bleach invitro. The DPPH radical potential was observed compared with treatment with 5, 10, 15, 20, 25 and 30µM doses of bryostatin1. Invivo, bryostatin1 prevented the TPA‑mediated increase in the level of H2O2 and myeloperoxidase in mouse epidermal tissue. Pretreatment of the mice with bryostatin 1 (30µM) followed by administration of TPA reduced the edema, as demonstrated via punched‑out mouse ear tissue, to 7.2mg, compared with 14mg in the TPA‑treated group. Treatment with bryostatin 1 prior to TPA administration markedly prevented the inflammation of the skin by inhibiting hyperplasia in the epidermal layer and the aggregation of inflammatory cells. The results demonstrated that treatment of mice with bryostatin1 at a 30µM dose prior to TPA administration significantly (P<0.005) inhibited the TPA‑mediated increase in the level of COX‑2. The activity of ornithine decarboxylase, increased by TPA, was additionally inhibited following pretreatment of the mice with bryostatin 1. In the mice treated with bryostatin 1 at 30µM doses prior to the administration of TPA, the appearance of papillomas was 20%, compared with 100% in the TPA group. Mice pretreated with bryostatin 1 at 30µM doses prior to TPA administration exhibited the appearance of 0.4 mean papillomas in each animal, compared with 5.2 in the TPA group. Therefore, the results of the present study demonstrated that bryostatin 1 inhibited the development and progression of tumors of skin in the mice, through the prevention of inflammation‑inducing processes and the quenching of radicals. Therefore, bryostatin1 maybe considered to be adrug of importance in the treatment of skin tumor.