Sinecatechins: Effects on HPV-Induced Enzymes Involved in Inflammatory Mediator Generation.

BACKGROUND

Based on published studies, the biological properties of green tea catechins are antiviral, antioxidative, anticarcinogenic, antiangiogenic, and immunostimulatory. The United States Food and Drug Administration has approved a topical ointment formulation of sinecatechins, derived from green tea catechins and other tea components, for the treatment of external genital and perianal warts. The exact mechanism of action of sinecatechins in eradication of human papillomavirus-induced external genital and perianal warts is unknown, but may be due to one or more of the mechanisms mentioned.

OBJECTIVE

This study was conducted to investigate the effects of sinecatechins on proteases, inflammatory enzymes, and kinases contributing to human papillomavirus expression and growth.

METHODS

Using commercially available in-vitro biochemical assays, sinecatechins were tested for their activity against matrix metalloproteinase (MMP-1, MMP-2, MMP-7, MMP-9); enzymes involved in oxidative stress (lipoxygenases and cyclooxygenases [COX-1, COX-2]); several growth factors (epidermal growth factor, platelet-derived growth factor, and transforming growth factor-β); and extracellular signal-regulated kinases 1/2. The ability of sinecatechins to inhibit ligand binding of growth factors was also studied.

RESULTS

Sinecatechins showed specific inhibition against a variety of enzymes at concentrations in the micromolar range. With the exception of matrix metalloproteinase-1, all proteases tested were inhibited in a dose-dependent manner. Pronounced inhibition of certain lipoxygenases was observed. Cyclooxygenases were also inhibited, with slight selectivity of greater inhibition against cyclooxygenases-2, the inducible form of cyclooxygenases. Extracellular signal-regulated kinases 1/2 (involved in human papillomavirus tumor cell growth) were also inhibited by sinecatechins at high concentrations, while epidermal growth factor receptor was inhibited at surprisingly low concentrations. In contrast, no inhibition of binding of various growth factors to their corresponding receptors was seen, highlighting the specificity of sinecatechins inhibitory activity. RESULTS demonstrated that sinecatechins specifically inhibit multiple human papillomavirus-induced pathways and molecules, likely contributing to external genital and perianal warts clearance via direct antiviral activity.

CONCLUSIONS

As expected, sinecatechins inhibited a broad range of enzymes and kinases involved in the generation of inflammatory mediators: proteases, oxygenases, and protein kinases were all inhibited by sinecatechins in the micromolar range.