Abstract #5520: Effect of Epigallocatechin 3-gallate (EGCG) and cancer chemotherapy on in vitro proliferation of chemoresistant, A375 human malignant melanoma

Green tea extracts (GTE) are taken for purported effects on tumor prevention and frequently prescribed by CAM practitioners for physiologic support, attenuation of treatment-related morbidities, and possible effects on tumor progression. EGCG, the most abundant polyphenol in GTE exerts the same effects which has facilitated its use in functional and molecular studies. Thus, EGCG has been shown to exert effects on numerous processes relevant to cancer growth including proliferation, differentiation, apoptosis, and modulation of oxidative reactions. EGCG has also been shown to enhance the activity of selected chemotherapeutic agents in pre-clinical models by different mechanisms suggesting that GTE may have efficacy in multidisciplinary treatment regimens. This would be especially attractive for the treatment of tumors considered to be intrinsically chemo-insensitive such as malignant melanoma (MM). Thus, the goal of the present study was to investigate the capacity of EGCG to collaborate with selected chemotherapeutic agents in mediating antiproliferative effects against the A375 MM cell line obtained from the American Type Culture Collection. Tumor proliferation was assessed spectrophotometrically with cells growing logarithmically by MTS assay. Tumor cells (5x10³ cells/well) in quadruplicate wells of a 96 well plate were incubated for 24-72 hours with pharmacologic concentrations of cisplatin, paclitaxel, or gemcitabine in the presence and absence of 21.8\#956;M EGCG selected to represent a concentration achieved by administration of 8, 200mg capsules daily of GTE which is consistent with prescribing patterns by most CAM practitioners for cancer patients. EGCG alone exerted an insignficant effect on A375 proliferation (94% of media control, ns). Similar results were obtained for cells incubated with Paclitaxel (1 ng/mL); Cisplatin (50 ng/mL); and gemcitabine (1 ng/mL) 88%, 97%, and 109% of media control values respectively, ns). In contrast, significant inhibition of proliferation was observed in cultures treated with EGCG in combination with either: Paclitaxel (69% of control, p=0.03); cisplain (76% of control, p=0.024); or gemcitabine (59% of control, p=0.006). Maximum inhibition of proliferation by ECGC in combination with each drug occured at 72 hrs but signficant inhibition at 48 hrs was also observed for combinations containing either paclitaxel or gemcitabine. The results of this exploratory study suggest that the intrinsic chemo-insensitivity of human malignant melanoma may be overcome by effects elicited by EGCG, the major polyphenol in GTE. Considering the lack of significant side effects and excellent tolerability of GTE, and the limited treatment options and poor prognosis for patients with malignant melanoma, combination regimens that include GTE are worth further innvestigation.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5520.