Retinoic Acid Reduces Stem Cell-Like Features in Pancreatic Cancer Cells.

Abstract

Retinoic acid (RA) has important functions during embryonic development being involved in cell growth and differentiation. Although approved for the treatment of acute promyelocytic leukemia, it is still under investigation for different solid tumors including pancreatic cancer. The objective of this study was to analyze how RA affects pancreatic cancer stem cells and how its combination with chemotherapy could impact cell growth. Using different pancreatic cancer cell lines, we evaluated the effect of RA alone or in combination with chemotherapy regulating cancer stem cells properties and pathways. Retinoic acid treatment reduces the expression of pancreatic stem cell markers CD24, CD44, CD133, and aldehyde dehydrogenase 1 but not c-Met. Although gemcitabine treatment increases the expression of some of these markers especially CD44 when it is combined with RA, a notable reduction in all of them is observed. Retinoic acid induces a G0/G1 arrest and combined with gemcitabine increases the apoptotic effect produced by chemotherapy probably as a consequence of a regulation of specific stem cell transcription factors. Retinoic acid regulates self-renewal capacity of cells in pancreatic tumors and should be further investigated in combination with chemotherapy as therapeutic strategy in pancreatic cancer.