EGCG, alone or combined with temsirolimus, inhibits tumor growth of sensitive and resistant HER2+ orthoxenopatients.

<p><b>(a)</b> Mice bearing HER2-PDX and resistant HER2-PDX (HER2-PDXR) were treated with control (C), EGCG (30 mg/kg, 3 days a week), temsirolimus (10 mg/kg, 1 day a week) or the combination (EGCG plus temsirolimus) for 21 days. Dots are mean of each experimental group and bars, SE. * (p ≤ 0.05), ** (p ≤ 0.01) and *** (p ≤ 0.001). <b>(b)</b> Apoptosis, by TUNEL fluorescent assay, was perfomed in control (C), EGCG (E), temsirolimus (T) and combination (T+E) treated as in (A) tumors. Tumors were collected at the end of the experiment and fixed in formalin. Pictures are representative of two samples of each group. <b>(c)</b> Body weight of the mice treated as in (A). Data are expressed as body weight at the end of the experiment and boxes show the 25th to 75th percentiles, whereas whiskers extend to the 5th and 95th percentiles.</p

FASN inhibitors improve pertuzumab and temsirolimus activity in parental and resistant cells.

<p><b>(a)</b> Cells were treated with pertuzumab (5 μg/ml) combined with EGCG (60 μM) or G28UCM (5 μM) for 5 days. Results were determined using an MTT assay and are expressed as ratio of inhibition of cell proliferation induced for each treatment alone versus inhibition induced for co- treatment from three independent experiments performed in triplicate. Dashed lines represent the effect of each drug alone, ratio 1. <b>(b)</b> Cells were treated with temsirolimus (0.05, 0.1, 0.5 and 1 μM) combined with EGCG (60 μM) or G28UCM (5 μM) for 2 days. Results were determined using an MTT assay and are expressed as ratio of inhibition of cell proliferation induced for each treatment alone versus inhibition induced for co- treatment from three independent experiments performed in triplicate and with several temsirolimus concentrations. Dashed lines represent the effect of each drug alone, ratio 1. * (p ≤ 0.05), ** (p ≤ 0.01) and *** (p ≤ 0.001) indicate levels of statistically significant difference compared with drugs administered alone.</p

EGCG, alone or combined with pertuzumab, inhibits tumor growth of sensitive and resistant HER2+ orthoxenopatients.

<p><b>(a)</b> Mice bearing HER2-PDX and resistant HER2-PDX (HER2-PDXR) were treated with control (C), EGCG (30 mg/kg, 3 days a week), pertuzumab (30 mg/kg, 1 day a week) or the combination (EGCG plus pertuzumab) for 24 days. Dots are mean of each experimental group and bars, SE. * (p ≤ 0.05), ** (p ≤ 0.01) and *** (p ≤ 0.001). <b>(b)</b> Apoptosis, by TUNEL fluorescent assay, was perfomed in control (C), EGCG (E), pertuzumab (P) and combination (P+E) treated as in (A) tumors. Tumors were collected at the end of the experiment and fixed in paraffin. Pictures are representative of two samples of each group. <b>(c)</b> Body weight of the mice treated as in (A). Data are expressed as body weight at the end of the experiment and boxes show the 25th to 75th percentiles, whereas whiskers extend to the 5th and 95th percentiles.</p

Pertuzumab plus trastuzumab combination improves effects in SK and SKLTR.

<p>Cells were treated with trastuzumab (20 μM), pertuzumab (5 μg/ml) and the combination of both for 5 days. Results were determined using an MTT assay and are expressed as the percentage of cell proliferation inhibition from three independent experiments performed in triplicate. Columns represent % of cell proliferation inhibition after trastuzumab or pertuzumab exposure and bars SE. * (p ≤ 0.05), ** (p ≤ 0.01) and *** (p ≤ 0.001) indicate levels of statistically significant difference compared with effect of the same drug in SKBr3 cells or compared with drugs administered alone (dashed line).</p

New Synthetic Inhibitors of Fatty Acid Synthase with Anticancer Activity

Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds <b>5</b>–<b>30</b> that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC₅₀ < 50 μM have been tested for their ability to inhibit FASN activity. Among them, derivative <b>30</b> blocks the 90% of FASN activity at low concentration (4 μM), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, <b>30</b> does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor <b>30</b> may aid the validation of this enzyme as a therapeutic target for the treatment of cancer