Zerumbone And Doxorubicin Combination Induces MAPK3 Dependent Apoptosis in Triple Negative Breast Cancer Cells

Aim Doxorubicin (DOX) is one of the most commonly used chemotherapeutic medications for treating several malignancies, including TNBC. However, severe toxicity and the development of resistance to drugs, limits its therapeutic index. As a result, there is a crucial need for the advancement of novel medications that boost the efficacy of Doxorubicin while decreasing its toxicity. Studies have shown that the Z. zerumbet -isolated sesquiterpene zerumbone (ZER) is a potent anti-proliferative molecule against several cancers including BC. This study intended to assess the antitumor activity of ZER in TNBC cells in combination with Doxorubicin. Methods MTT and Chou-Talay techniques were used to evaluate cell viability and pharmacodynamic interactions. Western blotting. flow cytometry, and fluorescence microscopy were used to assess the molecular mechanism underlying the anti-tumor activity of DOX-ZER combination. Results DOX and ZER combination significantly reduced the cell viability and showed synergistic impact on migration, proliferation, and colony formation potential of TNBC cells. Moreover, DOX-ZER combination resulted in enhanced ROS accumulation, activating MAPK3 mediated apoptosis and cell cycle arrest. Conclusions Our findings show that ZER is a potent anticancer molecule that may be used in combination with DOX to enhance therapeutic efficacy and reduce the development of therapeutic resistance.