Abstract 5610: Epigallocatechin 3-gallate (EGCG) as a natural product (NP) with potent antitumor activity against human ovarian cancer

Abstract

Abstract A substantial challenge in the practice of integrative cancer treatment is to identify active combinations of natural products (NPs) that can collaborate with conventional treatment modalities to achieve enhanced tumor control. This approach is especially attractive for tumors that are inherently chemoresistant or become chemoresistant as a consequence of multidrug resistance. But it has been difficult to prove efficacy of combining NPs with conventional treatment such as chemotherapy due in large part to the challenges inherent in conducting controlled clinical trials with combination regimens. These challenges provide a rationale for translational research studies to characterize effects of NPs on tumor processes relevant to chemoresistance. The current study investigated the activity of Epigallocatechin 3-gallate (EGCG), the principal polyphenol from green tea extract to modulate tumor proliferation and sensitivity to antitumor immunity in human ovarian cancer cells. Tumor proliferation was assessed with a standard MTS assay using the ATCC cell line, OvCar 3 as well as single cell suspensions prepared from human ovarian cancer surgical specimens. Sensitivity to IL2-activated human lymphocytes was assessed with a standard, 4 hr 51Chromium-release assay. EGCG produced a dose-dependent inhhibition of proliferation of the OvCar 3 cell line ranging from <5% (10 ug/mL) through 33% (30 ug/mL). Notably, these concentrations of EGCG are all achievable pharmacologically with a dose of 8, 200 mg capsules daily. Dose dependent inhibition of proliferation was also observed with cells from human ovarian cancer specimens with inhhibition ranging from 10.5% (5 ug/mL) to as much as 54% (25 ug/mL). The effects of EGCG were found to collaborate with pharmacologically achievable concentrations of both cisplatinum (Pt; 500 ng/mL) and gemcitabine (Gz; 10 ng/mL). Thus, 24%, 21% and 60% inhibition of OvCar 3 cells was observed with Pt, EGCG and Pt+EGCG respectively. The corresponding values were 30%, 34%, and 50% inhibition for Gz, EGCG, and Gz+EGCG. Additional effects of EGCG on OvCar 3 were shown in studies using EGCG pre-treatment of target cells prior to testing sensitivity to lysis by IL2-activated human lymphocytes. The results showed that EGCG pretreatment, in doses that did not reduce cell number or inhibit prolliferation over 72 hrs rendered the cells 53% more sensitive to lysis in the 51Chromium-release assay. These results demonstrate direct effects of the principal polyphenol of green tea extract on both the proliferative and immunologic sensitivitiy of human ovarian cancer cells. That these effects can collaborate with chemotherapeutic agents commonly used in the treatment of ovarian cancer patients suggests that combination regimens of this NP with cancer chemotherapy may be valuable in patients for both adjuvant therapy and for maintenance of remission. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5610.