Propolis: Intrinsic Pathway-Induced Apoptosis, G1 Cell Cycle Arrest, Reduced Chemotherapeutic Resistance in Adenocarcinoma, and Healthy Cell Preservation

Objective: This study investigated the potential synergistic effects of propolis, an antitumor and antioxidant natural product, and carboplatin, a frequently used chemotherapeutic agent for endometrial adenocarcinoma, one of the most common gynaecological cancers treatment. Materials and Methods: Ishikawa endometrial adenocarcinoma and healthy fibroblast (3T3) cell lines were treated with 0.5 mu L of carboplatin and 5 mu L of propolis. Cell count, viability, migration, ultrastructure, apoptosis, and cell cycle changes were assessed using cytological and immunocytochemical methods, flow cytometry, and transmission electron microscopy (TEM). Results: Propolis and carboplatin exhibited cytotoxic effects on Ishikawa cells. The combination of the two agents further reduced cell viability and migration. Propolis induced apoptosis through the intrinsic pathway and arrested the cell cycle in the G1 phase. TEM analysis revealed apoptosis in Ishikawa cells treated with propolis or carboplatin, while the carboplatin+propolis combination resulted in severe cell budding, apoptosis, and vacuolization. Migrasome-like structures were only observed in the Ishikawa carboplatin group. Minimal effects were observed on 3T3 cells. Conclusion: Propolis demonstrated cytotoxic, anti-proliferative, and proapoptotic effects on tumor cells without harming healthy cells. Its ability to prevent migrasome formation suggests it may reduce chemotherapeutic resistance. Therefore, propolis shows promise as a potential enhancer of anticancer treatments.