The combination of epigallocatechin gallate and curcumin suppresses ERα‐breast cancer cell growth in vitro and in vivo

Abstract

Both epigallocatechin gallate (EGCG) and curcumin have shown efficacy in various in vivo and in vitro models of cancer. This study was designed to determine the efficacy of these naturally derived polyphenolic compounds in vitro and in vivo, when given in combination. Studies in MDA-MB-231 cells demonstrated that EGCG 1 curcumin was synergistically cytotoxic and that this correlated with G 2 /M-phase cell cycle arrest. After 12 hr, EGCG (25 lM) 1 curcumin (3 lM) increased the proportion of cells in G 2 /M-phase to 263 6 16% of control and this correlated with a 50 6 4% decrease in cell number compared to control. To determine if this in vitro result would translate in vivo, athymic nude female mice were implanted with MDA-MB-231 cells and treated with curcumin (200 mg/kg/day, po), EGCG (25 mg/kg/day, ip), EGCG 1 curcumin, or vehicle control (5 ml/kg/day, po) for 10 weeks. Tumor volume in the EGCG 1 curcumin treated mice decreased 49% compared to vehicle control mice (p < 0.05), which correlated with a 78 6 6% decrease in levels of VEGFR-1 protein expression in the tumors. Curcumin treatment significantly decreased tumor protein levels of EGFR and Akt, however the expression of these proteins was not further decreased following combination treatment. Therefore, these results demonstrate that the combination of EGCG and curcumin is efficacious in both in vitro and in vivo models of ERa-breast cancer and that regulation of VEGFR-1 may play a key role in this effect. ' 2007 Wiley-Liss, Inc.

A new role for tamoxifen in oestrogen receptor-negative breast cancer when it is combined with epigallocatechin gallate

“…For example, EGCG (50 mg kg À1 , s.c.) was minimally effective at reducing tumour growth in a MDA-MB-231 xenograft model, but acetylating EGCG and thus turning it into a pro-drug enhanced its efficacy (Landis-Piwowar et al, 2007). In a similar xenograft model, the efficacy of EGCG was increased by the addition of curcumin (Somers-Edgar et al, 2008). However, the overall tumour volume was only decreased by 49% as compared with control after EGCG þ curcumin treatment, indicating that EGCG þ tamoxifen is a more effective combination therapy as tumour volume was decreased by 71% as compared with control.…”

“…Other studies have also shown that EGCG or green tea extract has a modest inhibitory effect on ER-negative tumour growth (Landis-Piwowar et al, 2007;Thangapazham et al, 2007;Somers-Edgar et al, 2008). For example, EGCG (50 mg kg À1 , s.c.) was minimally effective at reducing tumour growth in a MDA-MB-231 xenograft model, but acetylating EGCG and thus turning it into a pro-drug enhanced its efficacy (Landis-Piwowar et al, 2007).…”

“…In addition, the dose of EGCG (25 mg kg À1 , i.p.) was based on our previous study, which demonstrated that this dose was non-toxic and elicited a modest decrease in MDA-MB-231 tumour growth (Somers-Edgar et al, 2008). This dose is also twofold lower than that recently used in other ER-negative xenograft experiments with EGCG (Landis-Piwowar et al, 2007;Thangapazham et al, 2007).…”

“…Tamoxifen was given through oral gavage, whereas EGCG was given intraperitoneally. On the account of extensive first-pass metabolism (Li et al, 2001), EGCG is often administered parentally (Liao et al, 1995;Landis-Piwowar et al, 2007;Somers-Edgar et al, 2008). In addition, the dose of EGCG (25 mg kg À1 , i.p.)…”

“…Protein extraction from tumour tissue was performed as described (Somers-Edgar et al, 2008). The extracts or cell lysates were fractioned by SDS -PAGE, electrotransferred to nitrocellulose membranes, blotted with each antibody, and detected by amplified colour reagent (Bio-Rad, Auckland, New Zealand).…”