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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Polymeric black tea polyphenols inhibit mouse skin chemical carcinogenesis by decreasing cell proliferation
R Patel1, R Krishnan, A Ramchandani
1Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
Objectives:
The aim of this study was to investigate the antitumour promoting effects and possible mechanisms of action of the most abundant polymeric black tea polyphenols (PBPs 1-5) or thearubigins, in vivo.
Materials And Methods:
Effect of PBP pre-treatments on 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted skin papillomas was studied in 7,12-dimethylbenz(a)anthracene initiated mice over 40 weeks. Cell proliferation and apoptosis, in epidermis of the skin, were measured using appropriate immunohistochemical staining. Mitogen-activated protein kinase signalling studies were conducted with Western blot analysis at 10, 20, 30 and 40 weeks of promotion.
Results:
Pre-treatments with PBP fractions differentially altered latency, multiplicity and incidence of skin papillomas as compared to TPA treatments thereby exhibiting antipromoting effects. Most PBP fractions decreased TPA-induced cell proliferation by decreasing activation of signalling kinases (c-Jun N-terminal protein kinase, extracellular signal-regulated protein kinase, p38 protein kinase and Akt), transcription factors (activator protein-1 and nuclear factor kappa B) and inflammatory protein (cyclooxygenase 2). TPA-induced epidermal cell apoptosis was also decreased by pre-treatment with most PBP fractions. Higher levels of p53 and p21 in skin cells pre-treated with PBP fractions followed by TPA treatment as compared to only TPA-treated animals suggested possible activation of a cell cycle checkpoint.
Conclusions:
PBP-2 was observed to be the most potent polymeric polyphenol fraction and PBP-4 and PBP-5 showed only marginal activity, whereas PBP-1 and PBP-3 displayed intermediate efficacies. In conclusion, the protective effects of PBP fractions could be attributed to inhibition of TPA-induced cellular proliferation.
Insights
Black tea polyphenols (PBPs) show antitumour effects by inhibiting skin papilloma growth in mice. PBP-2 was most effective, reducing cell proliferation and activating cell cycle checkpoints, suggesting protective benefits.
Area of Science:
- * Oncology
- * Dermatology
- * Natural Products Chemistry
Background:
- * Black tea contains abundant polymeric polyphenols (PBPs), also known as thearubigins.
- * These compounds are investigated for their potential health benefits, including antitumour properties.
- * Understanding their mechanisms against chemically induced skin tumours is crucial.
Purpose of the Study:
- * To evaluate the in vivo antitumour promoting effects of PBPs (1-5) from black tea.
- * To elucidate the underlying mechanisms of action, focusing on cell proliferation and signalling pathways.
- * To identify the most potent PBP fraction for potential chemopreventive applications.
Main Methods:
- * A 40-week mouse skin papilloma model initiated with 7,12-dimethylbenz(a)anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).
- * Assessment of PBP fraction pre-treatments on tumour latency, multiplicity, and incidence.
- * Immunohistochemical analysis of cell proliferation and apoptosis; Western blot for mitogen-activated protein kinase signalling pathways.
Main Results:
- * PBP pre-treatments significantly altered skin papilloma development, demonstrating antipromoting effects.
- * Most PBP fractions reduced TPA-induced cell proliferation by inhibiting key signalling kinases (JNK, ERK, p38, Akt) and transcription factors (AP-1, NF-κB).
- * PBPs decreased TPA-induced apoptosis and increased p53 and p21 levels, suggesting cell cycle arrest.
Conclusions:
- * Polymeric black tea polyphenols exhibit significant antitumour promoting effects against skin papillomas in mice.
- * PBP-2 demonstrated the highest potency, with PBP-1 and PBP-3 showing intermediate efficacy, while PBP-4 and PBP-5 had marginal activity.
- * The protective effects are primarily attributed to the inhibition of TPA-induced cellular proliferation and modulation of related signalling pathways.
