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KMID : 0043320200430070735
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Archives of Pharmacal Research
2020 Volume.43 No. 7 p.735 ~ p.743
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ω-hydroxyundec-9-enoic acid induction of breast cancer cells apoptosis through generation of mitochondrial ROS and phosphorylation of AMPK
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Ahn Joung-Jwa
Kim Hye-Sung
Yang Kyung-Mi
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Abstract
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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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KEYWORD
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ω-hydroxyundec-9-enoic acid, AMPK, Mitochondria, ROS, Apoptosis, Breast cancer
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