Recently, it has been shown that protein phosphatase 2A (PP2A) dysfunction was common in many cancer types and was mediated by various inactivation mechanisms. Although many research studies observed antitumor effect of propolis extracts in various types of cancer, the mechanism of effect are still obscure. In this study, we investigated the effect of propolis on PPP2R1A expression and its relationship with apoptosis in the SW-620 (colorectal cancer), DU-145 and PC-3 (prostate cancer), and MCF-7 (breast cancer) cell lines, with WI-38 (healthy fibroblast) cells serving as the control. Moreover, we aimed to investigate the impact of propolis on apoptosis by analyzing apoptosis markers such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), APAF-1, and caspases-3, -8, and -9. Propolis samples were extracted, and their phenolic compounds were quantified using LC-MS/MS. The RealTime Cell Analysis System-xCELLigence (RTCA-SP) device and software were employed to assess cell viability and cytotoxicity of the propolis samples. The IC