Abstract
This study was performed to evaluate the anticancer effect of ω-hydroxyundec-9-enoic acid (ω-HUA), a microbial bio-catalyst product in breast cancer cells, through AMP-activated protein kinase (AMPK) regulation. ω-HUA mediated apoptosis was induced in breast cancer cells by AMPK activation, loss of mitochondrial membrane potential, and reactive oxygen species (ROS) generation. ω-HUA treatment of breast cancer cells increased the AMPK phosphorylation levels, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) proteins. In addition, anti-apoptotic members, such as Bcl-2, were downregulated, while Bax, a pro-apoptotic member, was upregulated. ω-HUA decreased the mitochondrial membrane potential while increasing the expression of cytochrome c (cyt c). Treating the cells with compound C, an AMPK inhibitor, reversed the phenomena, leading to an increase in cell viability and a decrease in apoptosis induction. Treating the cells with an ROS scavenger, N-acetyl cysteine (NAC), led to AMPK inactivation and apoptosis inhibition, allowing the recovery of cell health. In conclusion, ω-HUA sequentially caused the production of mitochondrial ROS and the consequent AMPK activation, thereby inducing apoptosis in breast cancer cells. Thus, ω-HUA may prove useful as an anticancer agent that targets AMPK in breast cancer cells.
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This study was supported by the Apple Tree Dental Hospital and Dr. S Medi Co., Ltd. (2020).
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Ahn, J., Kim, H. & Yang, K.M. ω-hydroxyundec-9-enoic acid induction of breast cancer cells apoptosis through generation of mitochondrial ROS and phosphorylation of AMPK. Arch. Pharm. Res. 43, 735–743 (2020). https://doi.org/10.1007/s12272-020-01254-x
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DOI: https://doi.org/10.1007/s12272-020-01254-x