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3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells

Ahmad, Aamir ; Ali, Shadan ; Ahmed, Alia ; Ali, Azfur S ; Raz, Avraham ; Sakr, Wael A ; Rahman, K M Wahidur Tan, Ming

PloS one, 2013-01, Vol.8 (1), p.e54657 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells
Autor: Ahmad, Aamir ; Ali, Shadan ; Ahmed, Alia ; Ali, Azfur S ; Raz, Avraham ; Sakr, Wael A ; Rahman, K M Wahidur
Tan, Ming
Assuntos: AKT protein ; Antibodies, Monoclonal, Humanized - pharmacology ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Breast cancer ; Breast Neoplasms - genetics ; Cancer ; Cancer cells ; Care and treatment ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Development and progression ; Drug development ; Drug resistance ; Drug Synergism ; ErbB-2 protein ; Female ; Forkhead Box Protein M1 ; Forkhead Transcription Factors - genetics ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Genomics ; Hematology ; Humans ; Indoles - pharmacology ; Kinases ; Medicine ; Metastases ; MicroRNAs ; MicroRNAs - genetics ; NF-κB protein ; Pancreatic cancer ; Pathology ; Patients ; Prostate cancer ; Receptor, ErbB-2 - genetics ; RNA Interference ; RNA Precursors ; Studies ; Toxicity ; Transfection ; Trastuzumab ; Tumor Stem Cell Assay ; Tumors
É parte de: PloS one, 2013-01, Vol.8 (1), p.e54657
Notas: Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: A. Ahmad KMWR. Performed the experiments: A. Ahmad SA A. Ahmed A. Ali KMWR. Analyzed the data: A. Ahmad SA A. Ahmed A. Ali KMWR. Contributed reagents/materials/analysis tools: A. Ahmad SA A. Ahmed A. Ali KMWR. Wrote the paper: A. Ahmad AR WAS KMWR.
Descrição: Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3'-diindolylmethane (DIM), a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing) and MDA-MB-468 (HER-2/neu negative) breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu.
Editor: United States: Public Library of Science
Idioma: Inglês

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3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells

Ahmad, Aamir ; Ali, Shadan ; Ahmed, Alia ; Ali, Azfur S ; Raz, Avraham ; Sakr, Wael A ; Rahman, K M Wahidur Tan, Ming

United States: Public Library of Science

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