Effect of Sinecatechins on HPV-Activated Cell Growth and Induction of Apoptosis.

BACKGROUND

Green tea catechins possess a wide range of pharmacological properties, including antiviral, anti-infective, and immunostimulatory properties. They also have demonstrated inhibitory effects on a variety of enzymatic and metabolic pathways involved in cancer development. Catechins have been shown to have antiproliferative properties in various cell lines and may have direct virucidal effect. 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 growth inhibitory potential of the sinecatechins in human cervical carcinoma cell lines infected with human papillomavirus.

METHODS

The viability of tumor cell lines (CaSki and SiHa infected with human papillomavirus-16; HeLa and C4-I infected with human papillomavirus-18) was investigated as one parameter in a short-term viability assay (48 hours). This was followed by a long-term clonogenic assay (12-23 days) to determine the cytotoxic potential of sinecatechins as a parameter for cell viability and proliferation. This assay determined if the effect observed in the viability assay was due to retardation in cell proliferation or to a reduction of total cell number, leading to cell death.

RESULTS

Based on the data collected, sinecatechins inhibited cell growth in all four tumor cell lines by 50 percent (GI(50)) at concentrations ranging from 160 to 360µM. C4-I cells were the most sensitive to treatment with sinecatechins, with a lower GI(50) (~34µM). Total GI was achieved in a 48-hour assay at 625µM sinecatechins (40µM for C4-I), with growth inhibitory potential detectable after one hour. Clonogenic assays confirmed the cytotoxic potential of sinecatechins with a reduction in clone numbers in a concentration-dependent fashion. Sinecatechins substantially reduced the number of surviving HeLa cells at a concentration of 200µM, while surviving SiHa cells were almost totally eradicated with a concentration of 600µM.

CONCLUSIONS

Sinecatechins demonstrated growth inhibitory potential in all four human papillomavirus-infected tumor cell lines, which may be attributed to the induction of apoptosis, mediated by cell cycle deregulation. In addition, this antiproliferative effect may contribute to the overall cancer-preventative function and possible direct antiviral activity of sinecatechins that may contribute to external genital and perianal warts clearance.