Background: Increased Ca2+ entry causes an increase in tumor cell proliferation, apoptosis, cytosolic reactive free oxygen species (cyROS), and mitochondrial ROS (miROS) in tumor cells. The cyROS and miROS stimulate the cation channels, including the TRPA1, TRPM2, and TRPV1. Sambucus ebulus L (SEB) (Dwarf Elder) induced both antioxidant and anticancer effects in the human hepatocarcinoma and human colon carcinoma cancer cell lines. We investigated the etiology of colorectal cancer and the impact of three channels, as well as the protective effects of SEB on apoptosis, cyROS, and miROS in the colon of mice with colitis-associated colon cancer (AOM/DSS). Methods: A total 28 mice were equally divided into four groups as control, SEB (100 mg/kg/day for 14 days), AOM/DSS, and SEB + AOM/DSS. Azoxymethane/dextran sulfate sodium-induced colon cancer associated with colitis was induced in the AOM/DSS groups within 10 weeks. At the end of the experiments, the colon samples were removed from the mice. Results: The protein bands of caspase − 3, TRPA1, TRPM2, and TRPV1 were increased by the treatments of AOM/DSS. The levels of apoptosis, cyROS, cleaved caspase − 3, and cleaved caspase − 9, as well as the depolarization of the mitochondrial membrane, all increased in the AOM/DSS group. Although they were reduced in the SEB and AOM/DSS + SEB groups by the treatments of SEB, TRPA1 (AP18), TRPM2 (ACA), and TRPV1 (capsazepine) antagonists, the apoptotic and oxidant values were further elevated in the AOM/DSS group by the treatments of TRPA1 (cinnamaldehyde), TRPM2 (H2O2), and TRPV1 (capsaicin) agonists. Conclusion: The activations of TRPA1, TRPM2, and TRPV1 channels induced the increase of apoptotic and oxidant actions in the colon cancer cells, although their inhibition via SEB treatment decreased the actions. Hence, TRPA1, TRPM2, and TRPV1 activations could be used as effective agents in the treatment of colon tumors.