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Purpose: To investigate whether formononetin exhibits antitumor activity in colorectal cancer cell lines via the mitochondria-dependent mitogen-activated protein kinase (MAPK) pathway.
Methods: Human colorectal cells were treated with various doses of formononetin for 24 h, followed by Cell Counting Kit-8 (CCK-8) assay and western blot. Human colorectal cells were incubated with equivalent vehicle (DMSO) or 100 μM formononetin for 24 h, followed by nuclear staining with propidium iodide (PI) and diamidino-2-phenylindole (DAPI) for analyses of apoptosis. Human colorectal cells were incubated with equivalent vehicle or 100 μM formononetin for 24 h followed by analysis of cell migration and invasion. Human colorectal cells were incubated with equivalent vehicle (DMSO) or 100 μM formononetin for various duration (3, 6, 12, and 24 h), followed by detection of intracellular reactive oxygen species (ROS) level and measurement of mitochondrial membrane potential (Δψm) to monitor mitochondria functionality.
Results: In human colorectal cancer cell lines SW1463 and T84, formononetin (> 20 μM) significantly inhibited cell growth (p < 0.05) in a dose-dependent manner, noticeably induced apoptosis, and suppressed cell migration and invasion. Western blot analysis revealed that formononetin treatment caused significantly increased levels of proapoptotic proteins, and suppression of cell proliferationrelated protein and matrix metallopeptidases (MMP) levels. Formononetin also induced mitochondrial depolarization and ROS generation in a time-dependent manner, indicating that formononetin mediates human colorectal cancer cell apoptosis via activation of MAPK pathway in a dose-dependent manner.
Conclusion: Formononetin induces human colorectal cancer cell apoptosis via mitochondriadependent MAPK pathway, thus lending experimental support for the clinical application of formononetin for colorectal cancer therapy.
Keywords: Formononetin, Colorectal cancer, Mitochondria, Reactive oxygen species, Cytochrome C, Mitogen-activated protein kinase