Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase theefficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth hasbeen identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanismsunderlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatmentof HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinctmodes of cell death and silences pro-survival signaling in HT-29 cells.