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COMBINED ANTICANCER ACTIVITY OF GEF GENE AND NOVEL CHEMOTHERAPEUTIC AGENTS ON MCF-7 BREAST CANCER CELLS

Houria Boulaiz, Juan Antonio Marchal, Alberto Ramirez, Jose Carlos Prados, Mª Celia Vélez Fernández, Macarena Perán, Ana Rama, Esmeralda Carrillo, Pablo Alvarez, Fernando Rodríguez-Serrano, Manuel Gallo, Antonio Espinosa, Joaquín Campos, Antonia Aránega


DOI: 10.4428/MMRR.p.201006001


Document Type: Poster


Date: Received 10th June 2010 20:21 UTC; Posted 10th June 2010 20:59 UTC


Subjects: Biotechnology, Cancer, Cell biology, Chemistry & Pharmacology, Gene transfer


Tags:   gene therapy   antitoumor activity



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Abstract:
In the last decade progress in diagnostic techniques and treatment has greatly contributed to the survival of cancer patients, however breast cancer is still one of the leading causes of death in women and its incidence in the developing world is on the rise. New therapeutic strategies are required to overcome the limitations of conventional breast cancer treatment. Thus, the use of novel antitumour drugs that are less toxic to normal tissues and more specific to malignant cells combined to suicide gene therapy offers a potential approach to this type of tumour. In this context, we have previously reported that gef gene found in E. coli encodes a small protein related with cell-killing functions, and benzomono and benzodi-heteropinics derivative compounds are regarded as potential anticancer agents. In this study, we analysed whether this novel antitumour drugs combined with gef gene treatment could result in enhanced citotoxicity in human tumour cell cultures. Combined treatment with recombinant retrovirus under the control of the tetracycline responsive element (TRE) expressing gef gene and benzomono and benzodi-heteropinics compounds clearly showed an additive cytotoxic effect on human MCF-7 cells. Doxycicline-induction of gef gene expression in MCF-7 cells combined with low doses of benzomono and benzodi-heteropinics derivatives compounds produced a significant decrease on proliferation rate and arrest cells in the G(0)/G(1) phase of the cell cycle. This inhibition was greater than that obtained using the gene therapy or chemotherapy alone. The combined action was dose-dependent in time. Moreover, Annexin-V-FITC and propidium iodide assays showed the presence of apoptotic and necrotic cell death, which was confirmed by both confocal and scanning electron microscopy. In conclusion, our results suggest that combined therapy with gef gene and new pharmacological derivatives has an important antitumour activity, due to the enhancement in the selective action of the pharmacological compounds by the gef gene expression. This new therapeutic strategy could be useful in the fight against breast cancer.
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