Sulindac sulfide attenuates cyclin D1 through Protein Kinase G pathway in SW480 colon cancer cells

초록

We studied the effect of sulindac sulfide in SW480 human colon cancer cells to determine the underlying molecular mechanism of colorectal cancer regression. The transcriptional regulators of cyclin D1, such as, c-fos, c-jun, SRE and TRE were studied by using the luciferase reporter assay. Our data suggest that sulindac sulfide decreases the enzymatic activity of subcellular cGMP-phosphodiesterase (PDE), thereby increasing intracellular levels of cGMP and PKG. Increased PKG downregulate the transcription of cyclin D1 when transiently transfected in SW480 cells. Constitutively active mutants of PKG showed marked transcriptional downregulation of c-fos in SW480 cells. We also found that the constitutively active mutants of PKG negatively regulate the activation of SRE and TRE, suggesting their involvement in the regulation of cyclin D1.