Proteomic Profiling of Trastuzumab (Herceptin(R))-Sensitive and -Resistant SKBR-3 Breast Cancer Cells.
Proteomic Profiling of Trastuzumab (Herceptin(R))-sensitive and -resistant SKBR-3 Breast Cancer Cells.
Filed under: Drug and Alcohol Rehabilitation
Anticancer Res. 2013 Feb; 33(2): 489-503
DI Cara G, Marengo G, Albanese NN, Marabeti MR, Musso R, Cancemi P, Pucci-Minafra I
The Human Epidermal Growth Factor Receptor 2 (HER-2), overexpressed in 25-30% of breast carcinomas (BC), is the therapeutic target for trastuzumab, a recombinant humanized monoclonal antibody. The initial response to trastuzumab is often followed by drug-insensitivity within one year. Several hypotheses have been raised to explain this event, but the mechanisms behind the responses to trastuzumab are still unclear. Aim: To study the effects of short and prolonged trastuzumab treatment on the proteomic profiles of HER-2-overexpressing SKBR-3 BC cells.Cells were treated with trastuzumab to obtain sensitive and resistant clones. The drug effects were evaluated at the phenotypical and proteomic levels.In the trastuzumab-resistant cells the expression of a large amount of proteins, initially affected by treatment, reverted to levels of the untreated cells.The results obtained so far illustrate for the first time a large-scale differential protein expression between trastuzumab-treated and untreated cells, and between trastuzumab-sensitive and resistant cells. We believe that the results obtained will help to increase the knowledge of the molecular effects of trastuzumab and will be useful to better-understand the drug resistance mechanisms.
HubMed – drug
Regulation of the Proliferation of Colon Cancer Cells by Compounds that Affect Glycolysis, Including 3-Bromopyruvate, 2-Deoxyglucose and Biguanides.
Filed under: Drug and Alcohol Rehabilitation
Anticancer Res. 2013 Feb; 33(2): 401-7
Lea MA, Qureshi MS, Buxhoeveden M, Gengel N, Kleinschmit J, Desbordes C
In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates.
HubMed – drug
ABCC4 Decreases Docetaxel and Not Cabazitaxel Efficacy in Prostate Cancer Cells In Vitro.
Filed under: Drug and Alcohol Rehabilitation
Anticancer Res. 2013 Feb; 33(2): 387-91
Oprea-Lager DE, Bijnsdorp IV, VAN Moorselaar RJ, VAN DEN Eertwegh AJ, Hoekstra OS, Geldof AA
This study aimed to investigate cabazitaxel efficacy in a model for docetaxel-resistant prostate cancer cells and to evaluate the involvement of ATP-cassette binding protein 4 (ABCC4) with regard to multidrug resistance.Docetaxel and cabazitaxel sensitivity was measured in PC3 and R3327-MATLyLu (MLL) cell lines, using the sulforhodamine B (SRB) assay. ABCC4 expression was examined by western blotting and its functional involvement in drug sensitivity by blocking with MK571 inhibitor.The docetaxel-resistant MLL cells (4.5-fold compared to cabazitaxel; p<0.001) were shown to express high levels of ABCC4, while non-resistant PC3 cells had no detectable ABCC4 expression. Functional inhibition of ABCC4 in MLL cells resulted in a two-fold decrease in effective concentration of docetaxel and had no effect on toxicity of cabazitaxel.Cabazitaxel showed an improved therapeutic efficacy over docetaxel in ABCC4-expressing prostate cancer cells. ABCC4 appears to be an important determinant of docetaxel resistance, since its inhibition almost completely reversed resistance. HubMed – drug
Fenbendazole as a potential anticancer drug.
Filed under: Drug and Alcohol Rehabilitation
Anticancer Res. 2013 Feb; 33(2): 355-62
Duan Q, Liu Y, Rockwell S
Background/Aims: To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes.We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens.Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation.These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation.
HubMed – drug
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