Gut Metabolite Indoxyl Sulfate Has Selective Deleterious and Anticancer Effect on Colon Cancer Cells

There are a number of reports about anticancer activity of indole derivatives. In this study, we investigated the role of indoxyl sulfate (IS) for its selective anticancer activity on colon cancer cells. IS treatment on HCT-116 and HT-29 human epithelial adenocarcinoma cells led to a decrease in cell proliferation, cell viability, and ATP content. Colon cancer cells showed a 10% increase in cell apoptosis in comparison to control. Due to IS treatment, cell morphology got distorted, cell number found decreased, intracellular vesicles formed, and cells were found floating in the media. Cells also showed a loss in membrane integrity and a decrease in colony-forming ability and ceased at the G2/M phase of the cell cycle. No significant change was noted in the level of inflammatory cytokines IL-17A, IL-1β, and TNF-α, histology, length of intestine, and spleen after 100 mM IS treatment to balb/c mice. These observations indicate the selective anticancer effect of IS on colon cancer cells.