The current evidence suggests that CYP2E1 and CYP1A2 activity is higher in males than females, while CYP3A, one of the most clinically relevant CYP isoforms, appears to have greater activity in females. Overall, more studies are needed to fully support these conclusions as there are many factors that influence drug metabolism and thus it is very difficult to isolate gender as a sole modulator of CYP activity.

No 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.

We have previously shown that tamoxifen þ epigallocatechin gallate (EGCG) is synergistically cytotoxic towards oestrogen receptor (ER)-negative breast cancer cells. To determine if this response would correlate with significant tumour suppression in vivo, athymic nude female mice were implanted with MDA-MB-231 cells and treated with tamoxifen, EGCG, EGCG þ tamoxifen, or vehicle control for 10 weeks. Tumour volume in EGCG-(25 mg kg À1 ) þ tamoxifen (75 mg kg À1 )-treated mice decreased by 71% as compared with vehicle control (Po0.05), whereas tumour weight was decreased by 80% compared with control (Po0.01). Epigallocatechin gallate treatment did not alter ER protein expression in MDA-MB-231 cells and thus was not a mechanism for the observed tumour suppression. However, western blotting of tumour extracts demonstrated that epidermal growth factor receptor (EGFR; 85% lower than control), pEGFR (78% lower than control), mammalian target of rapamycin (mTOR; 78% lower than control), and CYP1B1 (75% lower than control) were significantly lower after the combination treatment as compared with all other treatments. Nuclear factor-kB (NF-kB), b-Raf, p-MEK, S6K, 4EBP1, Akt, vascular EGFR-1 (VEGFR-1) and VEGF expressions were decreased in control but not in the individual treatments, whereas MEK, phospholipase D 1/2, TGFa, and ERK expressions were not changed after any treatment. The results demonstrate that tamoxifen at realistic doses (75 mg kg À1 ) can suppress the growth of ERnegative breast cancer when combined with EGCG. In addition, the dominant mechanism for tumour suppression is the concomitant decrease in tumour protein expressions of mTOR and the EGFR.