1,25-Dihydroxyvitamin D(3) enhances the susceptibility of anaplastic thyroid cancer cells to adriamycin-induced apoptosis by increasing the generation of reactive oxygen species

Anaplastic thyroid cancer (ATC) is a very aggressive malignancy that is resistant to various types of chemotherapy in humans. Most patients with late-stage ATC cannot undergo surgery and receive chemotherapy drugs. The present study investigated the influence of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) pretreatment on adriamycin (ADM) chemotherapy efficacy in the 8305c and 8505c ATC cell lines. The apoptotic effects of ADM on ATC cells pretreated with 1,25(OH)(2)D(3) were evaluated. Cell viability was identified by using the Cell Counting Kit-8 assay. Apoptosis was assessed by flow cytometry and staining with Hoechst 33342. The expression of the apoptotic protein cleaved caspase-3 was tested with a colorimetric assay kit and by western blotting. Reactive oxygen species (ROS) generation was assessed with the antioxidant N-acetyl-L-cysteine (NAC) and the assay H(2)-DCFDA. In addition, ROS production could be reversed by NAC treatment. The present study demonstrated that 1,25(OH)(2)D(3) enhanced ADM-induced apoptosis in 8305c and 8505c cell lines. Furthermore, 1,25(OH)(2)D(3) improved the ADM-induced ROS production and expression of cleaved caspase-3. NAC treatment inhibited the expression of cleaved caspase-3 in ATC cells, and reduced apoptosis in cells that were pretreated with 1,25(OH)(2)D(3) and ADM. These results demonstrated that 1,25(OH)(2)D(3) may enhance ADM-induced apoptosis by increasing ROS generation in ATC cells.