College of Food Science and Technology, Shenyang Agricultural University, Shenyang, China.
College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang, China.
Nat Prod Res. 2020 Mar;34(6):893-897. doi: 10.1080/14786419.2018.1508144. Epub 2018 Nov 16.
This study aims to isolate the potential antiproliferative and cytotoxic compounds from ginkgo biloba sarcotestas (GBS) and investigates the underlying mechanism in human MDA-MB-231 and mouse 4T-1 triple-negative breast cancer cells. Our results showed that 2-Hydroxy-6-tridecylbenzoic acid was isolated by cytotoxicity-guided fractionation where different fractions were assessed using MTT assay against MDA-MB-231 and 4T-1 cells. Colony formation assay showed that 2-Hydroxy-6-tridecylbenzoic acid significantly inhibited cell proliferation. The inhibition was associated with the enhancement of cytochrome P450 (CYP) 1B1 expression in a dose- and time-dependent manner and no significant change of CYP1A1 expression by qPCR and Western blot assays in MDA-MB-231 and 4T-1 cells. The mechanism was further demonstrated by the activation of aryl hydrocarbon receptor (AhR) pathway with the upregulation of AhR, AhR nuclear translocator (ARNT) and AhR-dependent xenobiotic response elements (XRE) activity. These findings may have implications for development of anticancer agents containing 2-Hydroxy-6-tridecylbenzoic acid as functional additives.
本研究旨在从银杏外种皮（GBS）中分离潜在的抗增殖和细胞毒性化合物，并研究其在人 MDA-MB-231 和小鼠 4T-1 三阴性乳腺癌细胞中的作用机制。我们的研究结果表明，通过细胞毒性导向分离出 2-羟基-6-十三烷基苯甲酸，通过 MTT 法评估不同馏分对 MDA-MB-231 和 4T-1 细胞的活性。集落形成实验表明，2-羟基-6-十三烷基苯甲酸能显著抑制细胞增殖。这种抑制作用与细胞色素 P450（CYP）1B1 的表达增强有关，呈剂量和时间依赖性，qPCR 和 Western blot 分析表明在 MDA-MB-231 和 4T-1 细胞中 CYP1A1 的表达没有明显变化。该机制通过芳基烃受体（AhR）途径的激活进一步得到证实，AhR、AhR 核转位蛋白（ARNT）和 AhR 依赖性外源物质反应元件（XRE）活性上调。这些发现可能对开发含有 2-羟基-6-十三烷基苯甲酸作为功能添加剂的抗癌药物具有重要意义。
