Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt, Germany; LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Frankfurt, Germany.
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Frankfurt, Germany; Institute of Pharmaceutical Biology, Faculty of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt, Frankfurt, Germany.
Biomed Pharmacother. 2022 Apr;148:112734. doi: 10.1016/j.biopha.2022.112734. Epub 2022 Feb 18.
Lichen extracts containing, among other compounds, depsides such as evernic acid, atranorin, and lecanoric acid possess anti-proliferative effects. We aimed to identify lichen metabolites that are responsible for the observed anti-proliferative effects. We performed cytotoxicity, cell colony, cell cycle and apoptosis assays in various cell lines or primary immune cells. We analyzed several cell cycle proteins and apoptosis-related proteins to gain insights into the underlying mechanism. All depsides reduced the viability of the tested cell lines (HCT-116, HEK293T, HeLa, NIH3T3, RAW246.7) in a cell line-dependent manner with lecanoric acid being the most effective. Atranorin did not influence the cell cycle or colony formation in HCT-116 cells, but induced apoptosis in HCT-116 cells. Evernic acid showed no anti-proliferative effects. Lecanoric acid inhibited cell colony formation already at 0.03 µg/ml in HCT-116 cells and induced a G2 cell cycle block in several cell lines. Moreover, lecanoric acid arrested the cell cycle, presumably in the M phase, since expression of cyclin B1 and phosphorylated histone H3 was upregulated, whereas the inactive cyclin-dependent kinase 1 (CDK1) was reduced in HCT-116 cells. Most importantly, cell death induced by lecanoric acid was more prominent in cancer cells than in primary human immune and endothelial cells. In conclusion, lecanoric acid seems to mediate its anti-proliferative effects via arrest of cells in the M phase. Our data suggest lecanoric acid may be a potential new candidate for anti-cancer therapy, because it has anti-proliferative effects on cancer cell lines, and does not affect primary immune cells.
含有地衣酚类化合物（如地衣酸、扁枝衣酸和栓菌酸）的地衣提取物具有抗增殖作用。我们旨在确定负责观察到的抗增殖作用的地衣代谢物。我们在各种细胞系或原代免疫细胞中进行了细胞毒性、细胞集落、细胞周期和细胞凋亡测定。我们分析了几种细胞周期蛋白和凋亡相关蛋白，以深入了解潜在的机制。所有的地衣酚类化合物均以细胞系依赖性方式降低了测试细胞系（HCT-116、HEK293T、HeLa、NIH3T3、RAW246.7）的活力，其中栓菌酸的效果最为显著。扁枝衣酸不会影响 HCT-116 细胞的细胞周期或集落形成，但会诱导 HCT-116 细胞凋亡。地衣酸没有显示出抗增殖作用。栓菌酸在 0.03 µg/ml 时就已经抑制了 HCT-116 细胞的集落形成，并在几种细胞系中诱导了 G2 细胞周期阻滞。此外，栓菌酸使细胞周期停滞，推测是在 M 期，因为 cyclin B1 和磷酸化组蛋白 H3 的表达上调，而无活性的细胞周期蛋白依赖性激酶 1（CDK1）在 HCT-116 细胞中减少。最重要的是，栓菌酸诱导的细胞死亡在癌细胞中比在原代人免疫细胞和内皮细胞中更为明显。总之，栓菌酸似乎通过将细胞阻滞在 M 期来介导其抗增殖作用。我们的数据表明，栓菌酸可能是一种新的抗癌治疗的潜在候选药物，因为它对癌细胞系具有抗增殖作用，并且不影响原代免疫细胞。
