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

Zeng,Ning; Xu,Yi; Wu,Yiping; Hongbo,Tang; Wu,Min

doi:10.3892/mmr.2017.7993

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

Authors:
- Ning Zeng
- Yi Xu
- Yiping Wu
- Tang Hongbo
- Min Wu
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Affiliations: Department of Plastics and Aesthetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/mmr.2017.7993
Pages: 1077-1082

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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 in vitro. The DPPH radical potential was observed compared with treatment with 5, 10, 15, 20, 25 and 30 µM doses of bryostatin 1. In vivo, bryostatin 1 prevented the TPA‑mediated increase in the level of H2O2 and myeloperoxidase in mouse epidermal tissue. Pretreatment of the mice with bryostatin 1 (30 µM) followed by administration of TPA reduced the edema, as demonstrated via punched‑out mouse ear tissue, to 7.2 mg, compared with 14 mg 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 bryostatin 1 at a 30 µM 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 30 µM 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 30 µM 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, bryostatin 1 maybe considered to be adrug of importance in the treatment of skin tumor.

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