College of Food Science and Technology, Shenyang Agricultural University, Shenyang, China.
College of Food Science and Engineering, Bohai University, Jinzhou, China.
Nat Prod Res. 2021 Dec;35(24):5924-5928. doi: 10.1080/14786419.2020.1803310. Epub 2020 Aug 11.
2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients.
2-羟基-6-十三烷基苯甲酸是烷基水杨酸单体化合物,大量存在于银杏叶提取物中,但它在三阴性乳腺癌(TNBC)中的抗迁移和抗侵袭作用的潜在机制尚不清楚。在这里,2-羟基-6-十三烷基苯甲酸抑制 MDA-MB-231 和 4T-1 细胞的生长,而对 MCF-10A 正常乳腺细胞没有毒性。同时,2-羟基-6-十三烷基苯甲酸抑制细胞迁移和侵袭,以及 EMT,伴随着 E-钙黏蛋白表达的增加,N-钙黏蛋白、波形蛋白、Snail、MMP-2 和 MMP-9 表达的减少。这种抑制作用通过激活 MDA-MB-231 和 4T-1 细胞中的 AMP 激活蛋白激酶(AMPK)来增强细胞色素 P450(CYP)1B1 的表达进一步得到证实。用 siRNA 沉默 CYP1B1 和 AMPK 可阻断迁移和侵袭的抑制作用,并逆转 EMT 相关基因。这些发现可能为 2-羟基-6-十三烷基苯甲酸作为 TNBC 患者的靶向治疗药物提供了一种新的机制。