Paclitaxel inhibits autophagy in breast cancer cells
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Abstract
Taxanes are used for the treatment of breast, ovarian, and lung cancer. Unfortunately, taxane based therapy—the current treatment for metastatic breast cancer—has substantial shortcomings including myelosupression, neurotoxicity, and frequently acquired resistance. Our present understanding of taxane cytotoxicity is incomplete and prevents rational approaches to taxane improvement. Autophagy is a celluar process that digests portions of the cytosol to provide metabolic support in times of stress. This process is capable of promoting survival or conversely promoting cell death, depending on the context. The relationship between paclitaxel and autophagy is unclear. In this study, we show that paclitaxel causes inhibition of autophagy in breast cancer cells, both by decreasing autophagosome formation and by altering autophagosome trafficking and localization. Autophagy inhibition protects breast cancer cells against paclitaxel induced cell death, suggesting that manipulation of autophagy may represent a therapeutic target for improving breast cancer treatment options.