Abstract 2105: Evaluation of antitumor properties of metformin over human multidrug-resistant chronic myeloid leukemia cells

Abstract

Abstract Besides the progress in the knowledge of cancer biology, the rates of mortality due to this disease are still considerably elevated. Therefore, application of new drugs in antitumor therapies has been constantly studied. However, any of them have achieved a considerable success so far. In this work we evaluated the ability of metformin, a traditional hypoglycemic prescribed to treatment of type II diabetes along decades, over programmed cell death and modulation of metastatic potential in multidrug resistant (MDR) human myeloid chronic leukemia cells (Lucena), through MTT reduction test, flow cytometry, western blotting and gelatin zymography. Metformin was able to reduce the cell viability in a concentration and time-dependent manner, but was not able to induce Lucena cells to apoptosis or necrosis, though activation of the apoptotic machinery. Indeed, it was not observed activation of caspase 3, in contrast to an expressive activation of PARP. Interestingly, proteins associated to autophagy were overexpressed by Lucena cells, and an arrest of cell cycle was observed after exposition to the drug. Finally, it was verified that metformin was able to modulate activity of MMP2 and MMP9, enzymes associated to the metastatic process. Taken together these results suggest that the hypoglycemic is able to acts over the first steps of cancers in more aggressive stages. Finally, inhibition of MMPs indicates a promissory action of metformin for the treatment of metastatic disease. Note: This abstract was not presented at the meeting. Citation Format: Ligia P. Oliveira, Débora L. Renó, Rodrigo S. Curvello, Luana P. Lima, Ana Carolina S. Galvão. Evaluation of antitumor properties of metformin over human multidrug-resistant chronic myeloid leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2105. doi:10.1158/1538-7445.AM2017-2105