Objectives The long-term and high-dose use of doxorubicin as chemotherapy for triple-negative breast cancer (TNBC) patients induces epithelial-to-mesenchymal transition (EMT) and stimulates cancer metastasis. Cinnamaldehyde is a major compound of cinnamon oil (CO) suppressing Snail and NFκB activity that are involved in cell migration. This study aims to explore the activity of CO as a co-chemotherapeutic agent on 4T1 breast cancer cells. Methods The CO was obtained by water and steam distillation and was characterized phytochemically by gas chromatography-mass spectrometry (GC-MS). Cytotoxic activity of single CO or in combination with doxorubicin was observed by MTT assay. Cell migration and MMP-9 expression were measured by scratch wound healing and gelatin zymography assays. The intracellular reactive oxygen species (ROS) levels were observed by 2′,7′–dichlorofluorescin diacetate (DCFDA) staining flowcytometry. Results The phytochemical analysis with GC-MS showed that CO contains 14 compounds with cinnamaldehyde as the major compound. CO exhibited cytotoxicity on 4T1 cells with the IC50 value of 25 μg/mL and its combination with doxorubicin decreased cell viability and inhibited cell migration compared to a single use. Furthermore, the combination of CO and doxorubicin inhibited MMP-9 expression and elevated intracellular ROS levels compared to control. Conclusion CO has the potential to be developed as a co-chemotherapy agent through inhibition of cell migration, and intracellular ROS levels elevation.
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