Columbianadin (CBN) effectively suppresses the growth of colon cancer cells. Low concentration (up to 25 μM) of Columbianadin induces apoptosis, and high concentration (50 μM) of Columbianadin induces necroptosis. The induction of apoptosis by Columbianadin is correlated with the modulation of caspase-9, caspase-3, Bax, Bcl-2, Bim and Bid, and the induction of necroptosis is related with RIP-3, and caspase-8. In addition, Columbianadin induces the accumulation of ROS and imbalance in the intracellular antioxidant enzymes such as SOD-1, SOD-2, catalase and GPx-1. Columbianadin shows the most effective growth inhibitory activity against human colorectal cancer cells. Accordingly, further study is performed using HCT116 cells to give the detailed growth-inhibitory mechanism of action mediated by Columbianadin. The cells treated with various concentrations of Columbianadin (0-100 μM) exhibit a dose- and time-dependent growth inhibition with an IC50 value of 47.2 and 32.4 μM after 48 and 72 h incubation, respectively. Treatment of various concentrations (12.5, 25, and 50 μM) of Columbianadin for 48 h in HCT116 cells decreases the number of cells and increases the floating cells. Apparent morphological changes with round-shape and dying cells are also observed at 25 and 50 μM Columbianadin -treated cells.