Photodynamic therapy in combination with green tea polyphenol including EGCG enhances antitumor efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cells

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A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), has been known to possess anti-inflammatory, anti-tumor, anti-oxidant, and anti-angiogenic properties. A biological significance of photodynamic therapy (PDT) with EGCG was investigated in TC-1 tumor cell implanted mice were examined.

The anti-proliferative effects by the combination of PDT (Radachlorin 2.5 μg/ml, 6.25 J/cm²) and EGCG were examined by use of TC-1 Cells, a cell line that expresses HPV16 E6 and E7 proteins. In C57BL/6 mice implanted TC-1 cells, a cell line that expresses HPV16 E6 and E7 proteins when the tumor sized is increased to 200 - 250 mm³. The mice were randomly divided into four groups of Negative control, PDT, EGCG and PDT + EGCG (n = 7). The tumor were then daily administered EGCG (200, 400 mg/kg body wt) after given external light treatment (Radachlorin 10 mg/kg body wt, 300 J/cm²).

To evaluate in vitro, in vivo anti-tumor effects, we investigated western blot assay using COX-2, MMP9, VEGF antibody.

PDT or EGCG was found to be more effective compare with non-treated group. Moreover, PDT combined with EGCG demonstrated a significant suppression of cell growth and tumor growth. In groups treated with Radachlorin/PDT + EGCG, the cell growth was significantly suppressed by 47.7%, 66.0% and 87.0% or 60.0%, 79.3% and 90.7% respectively. in comparison with the Radachlorin/PDT or EGCG alone group (P < 0.05). The tumor growth was significantly suppressed by 77.3%, 85.7%, 88.9%, and 84.0% at 3, 6, 19, 21 days after the treatment, respectively of suppression compared with the control group. and 70.2%, 76.1%, 74.7% and 62.2% or 71.7% 71.3%, 68.9% and 57.9% respectively, in comparison with the Radachlorin/PDT or EGCG alone group (P < 0.0001). The PDT combination with EGCG in vitro and in vivo led to a significant decrease in levels of COX-2, MMP9, VEGF at 48 hr post PDT plus EGCG combination treatment.

These data suggest that EGCG can inhibit cells growth and tumor growth. In TC-1 cell and TC-1 transplanted mice, tumor cell growth and tumor growth was significantly regressed by Radachlorin/PDT combinated with EGCG therapy in comparison with PDT or EGCG alone group.