ABSTRACT
Tumor recurrence is now the leading cause of breast cancer-related death. These recurrences are believed to arise from residual cancer stem cells that survive initial therapeutic intervention. Therefore, a comprehensive understanding of cancer stem cell biology is needed to generate more effective therapies. Here we investigate the association between dysregulation of lipid metabolism and breast cancer stem cells. Focusing specifically on lipid droplets, we found that the lipid droplet number correlates with stemness in a panel of breast cell lines. Using a flow cytometry-based method developed for this study, we establish a means to isolate cells with augmented lipid droplet loads from total populations and show that they are enriched in cancer stem cells. Furthermore, pharmacological targeting of fatty acid metabolism reveals a metabolic addiction in a subset of cell lines. Our results highlight a key role for the lipid metabolism in the maintenance of the breast cancer stem cell pool, and as such, suggest it as a potential therapeutic target.
ABSTRACT
The present study characterized propolis extracts produced by Scaptotrigona bipunctata (Tubuna) and Melipona quadrifasciata (Mandaçaia) by LC-MS/MS; their cytotoxicity as well as the mechanism of action in a melanoma cellular model were also assessed. The chemical characterization performed by UPLC-ESI-QTOF/MS2 analysis revealed uncommon presence of piperidinic alkaloids in Tubuna's propolis extract together with C-glycopyranoside flavonoids. Mandaçaia's propolis collected in the same area rather presented terpenoids and flavonoids. Regarding the mechanism of cytotoxicity, propolis extracts increased the accumulation of reactive oxygen species (ROS), reduced the potential of mitochondrial membrane, induced a decrease in the proteins Bcl-2 and AKT-3 levels, and decreased melanoma cells' migration and invasion. Both propolis extracts induced apoptosis while only Mandaçaia's propolis extract induced cell cycle arrest in G2/M.
