The present study examines whether 1,5,8-tri-hydroxy-3-methoxy xanthone (TMX) isolated from Swertia chiratacould restrict colon cancer cells by downregulatingproliferation and inducing apoptosis. The chemotherapeuticactivity of TMX was evaluated in several coloncancer and normal cell lines using in vitro assays likeMTT assay, cell-cycle analysis, caspase-3 activity assay,annexin V/PI staining, JC10 assay, intracellular reactiveoxygen species (ROS) level determination by dicholorofluoresceindi-acetate (DCFH-DA). The present studyrevealed that TMX from S. chirata could effectivelyinhibit proliferation of metastatic colon cancer celllines. The chemotherapeutic potential of TMX againstmetastatic colon cancer cell lines was achieved bydownregulating several critical regulatory genes enablingthe suppression of the proliferative potential ofcolon cancer cells and driving them towards apoptosisin a ROS dependent manner. In addition, TMX showedchemosensitization potential in colon cancer cell lines © 2022, Current Science. All Rights Reserved.