An extract of the bark of Khaya senegalensis is commonly used in African traditional medicine for pain and inflammation. Khaya senegalensis bark extract (KSBE) was hypothesized to contain inhibitors of the cyclooxygenase-2 (COX-2) gene and to be useful in the prevention and treatment of colorectal cancer. The diphenyl-2-picrylhydrazyl (DPPH)- free radical activity and the total phenolic content of KSBE were measured, followed by an investigation of cell growth inhibition, COX and prostaglandin E 2 (PGE2) suppression, as well as apoptosis by Western blot analysis and ELISA. Our data clearly showed that KSBE displays anti-proliferative, antiinflammatory and pro-apoptotic effects on HT-29, HCT-15 and HCA-7 cells. Since all three cell lines, irrespective of COX-2 status (HCT-15 is COX-2-deficient), were affected by the treatment, it can be concluded that both COX-dependent and COX-independent pathways are activated by KSBE.