BACKGROUND Epithelial ovarian cancer is a major cause of mortality in women and one of the most common gynecologic disorders. Pterostilbene (PTS), a trans-3,5-dimethoxy-4'-hydroxystilbene, was chosen for this work due to its reported effectiveness as a chemotherapeutic agent in cancer studies. In this work, we studied underlying molecular mechanisms of PTS treatment in various ovarian cancer cell lines such as OVCAR8, OV1063, IGROV-1, and SKOV3. MATERIAL AND METHODS We used the cytometric bead array (CBA) method and real-time PCR analysis to analyze the secretion level of tumor necrosis factor alpha (TNF-α) and to measure the TNF-α mRNA expression. NF-kappa B (NF-κB) promoter analysis, Western blot analysis, electrophoresis mobility shift assay (EMSA), and immunostaining analyses were performed to measure the NF-κB activity and other relative proteins levels. RESULTS The PTS treatment decreased the release of TNF-α in IGROV-1 ovarian cancer cells. It also showed significant inhibitory effect on nuclear NF-κB p50, and NF-κB p65 protein levels. CONCLUSIONS From the results obtained, we suggest that PTS has the potential to treat ovarian cancer by reducing the level of TNF-α cytokine and to have a limited effect on NF-κB, AKT, and ERK signaling pathways.