Department of Food Science and Industry, Jungwon University, 85, Munmu-ro, Goesan-eup, Goesan-gun, Chungcheongbuk-do, 28024, Republic of Korea.
Institute of Biomedical Science, Apple Tree Dental Hospital, 1450, Jungang-ro, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 10387, Republic of Korea.
Arch Pharm Res. 2020 Jul;43(7):735-743. doi: 10.1007/s12272-020-01254-x. Epub 2020 Jul 27.
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.
本研究旨在通过调节 AMP 激活的蛋白激酶（AMPK）来评估 ω-羟基十一碳烯酸（ω-HUA）作为一种微生物生物催化剂产物在乳腺癌细胞中的抗癌作用。ω-HUA 通过激活 AMPK、线粒体膜电位丧失和活性氧（ROS）的产生诱导乳腺癌细胞凋亡。ω-HUA 处理乳腺癌细胞可增加 AMPK 磷酸化水平、切割的半胱天冬酶-3 和多聚（ADP-核糖）聚合酶（PARP）蛋白。此外，抗凋亡成员如 Bcl-2 下调，而促凋亡成员 Bax 上调。ω-HUA 降低线粒体膜电位，同时增加细胞色素 c（cyt c）的表达。用 AMPK 抑制剂化合物 C 处理细胞可逆转这些现象，导致细胞活力增加和凋亡诱导减少。用 ROS 清除剂 N-乙酰半胱氨酸（NAC）处理细胞可导致 AMPK 失活和凋亡抑制，使细胞恢复健康。总之，ω-HUA 依次引起线粒体 ROS 的产生和随后的 AMPK 激活，从而诱导乳腺癌细胞凋亡。因此，ω-HUA 可能被证明是一种有用的抗癌剂，可作为乳腺癌细胞中 AMPK 的靶点。
