Zerumbone, a sesquiterpene occurring in zingiberaceous plants in Southeast Asian countries, has been shown to have anti-inflammatory effects in several independent experimental studies. We examined its effect on the expression of proinflammatory genes in human colon adenocarcinoma cell lines, Caco-2, Colo320DM, and HT-29, using reverse transcription-polymerase chain reaction (RT-PCR) assays. Surprisingly, zerumbone markedly induced the expression of interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in each cell line in concentration- and time-dependent manners. Results of a previous pharmacological approach using specific inhibitors of mitogen-activated protein kinases (MAPKs) suggested that the activation of both c-Jun N-terminal kinase and extracellular signal-regulated protein kinase, however, not that of p38 MAPK, may be involved in zerumbone-induced IL-1beta expression pathways in Caco-2 cells. The present results imply that zerumbone increases the production of proinflammatory cytokines in cancerous tissues in the colon and that this biochemical property may cause side-effects.