Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland.
Independent Laboratory of Natural Products Chemistry, Medical University of Lublin, 20-093 Lublin, Poland.
Molecules. 2020 Apr 28;25(9):2046. doi: 10.3390/molecules25092046.
Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of L. or L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including . As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.
天然存在的香豆素是广泛用于亚洲传统医学的生物活性化合物。它们已被证明能抑制增殖、诱导细胞凋亡和/或增强目前用于治疗各种癌细胞类型的药物的细胞毒性。我们的研究目的是研究不同线性呋喃香豆素对人横纹肌肉瘤、肺癌和喉癌癌细胞系的增殖抑制活性，并阐明其细胞作用机制。香豆素是从 L. 或 L. 的果实中分离得到的，并使用高效逆流色谱（HPCCC）进行分离。通过 HPLC-DAD 和 NMR 分析确认分离化合物的结构和纯度。通过甲基噻唑基二苯基四唑溴化物（MTT）和乳酸脱氢酶（LDH）测定分别评估细胞活力和毒性。通过流式细胞术分析测量细胞凋亡和细胞周期进程的诱导。应用 qPCR 方法检测基因表达的变化。线性呋喃香豆素以剂量依赖的方式抑制具有不同化合物和癌细胞类型特异性的癌细胞增殖。由于与特定基因表达变化相关的细胞周期进程的抑制，尤其是 的变化，欧前胡素（IMP）对人横纹肌肉瘤和喉癌细胞系表现出最强的生长抑制作用。由于 IMP 对正常细胞似乎没有毒性，而目前尚无专门用于喉鳞状细胞癌和横纹肌肉瘤的化疗方法，因此我们的结果可能为寻找有效的抗癌药物开辟了新的方向。
