Buachan Paiwan, Namsa-Aid Maneekarn, Sung Hye Kyoung, Peng Chun, Sweeney Gary, Tanechpongtamb Wanlaya
Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
Oncol Rep. 2021 Jun;45(6). doi: 10.3892/or.2021.8045. Epub 2021 Apr 13.
Cancer metastasis is the leading cause of mortality in cancer patients. Over 70% of lung cancer patients are diagnosed at advanced or metastatic stages, and this results in an increased incidence of mortality. Terrein is a secondary bioactive fungal metabolite isolated from . Numerous studies have demonstrated that terrein has anticancer properties, but in the present study, the cellular mechanisms underlying the inhibition of lung cancer cell metastasis by terrein was investigated for the first time. Using MTT assays, the cytotoxic effects of terrein were first examined in human lung cancer cells (A549 cells) and then compared with its cytotoxic effects in three noncancer control cell lines (Vero kidney, L6 skeletal muscle and H9C2 cardiomyoblast cells). The results indicated that terrein significantly reduced the viability of all these cells but exhibited a different level of toxicity in each cell type; these results revealed a specific concentration range in which the effect of terrein was specific to A549 cells. This significant cytotoxic effect of terrein in A549 cells was verified using LDH assays. It was then demonstrated that terrein attenuated the proliferation of A549 cells using IncuCyte image analysis. Regarding its antimetastatic effects, terrein significantly inhibited A549 cell adhesion, migration and invasion. In addition, terrein suppressed the angiogenic processes of A549 cells, including vascular endothelial growth factor (VEGF) secretion, capillary‑like tube formation and VEGF/VEGFR2 interaction. These phenomena were accompanied by reduced protein levels of integrins, FAK, and their downstream mediators (e.g., PI3K, AKT, mTORC1 and P70S6K). All these data indicated that terrein was able to inhibit all the major metastatic processes in human lung cancer cells, which is crucial for cancer treatment.
癌症转移是癌症患者死亡的主要原因。超过70%的肺癌患者在晚期或转移阶段被诊断出来，这导致死亡率上升。土曲霉毒素是从……中分离出的一种次生生物活性真菌代谢产物。许多研究表明土曲霉毒素具有抗癌特性，但在本研究中，首次对土曲霉毒素抑制肺癌细胞转移的细胞机制进行了研究。使用MTT法，首先在人肺癌细胞（A549细胞）中检测土曲霉毒素的细胞毒性作用，然后将其与在三种非癌对照细胞系（Vero肾细胞、L6骨骼肌细胞和H9C2心肌母细胞）中的细胞毒性作用进行比较。结果表明，土曲霉毒素显著降低了所有这些细胞的活力，但在每种细胞类型中表现出不同程度的毒性；这些结果揭示了一个特定的浓度范围，在该范围内土曲霉毒素对A549细胞具有特异性作用。使用LDH法验证了土曲霉毒素在A549细胞中的这种显著细胞毒性作用。然后使用IncuCyte图像分析证明土曲霉毒素减弱了A549细胞的增殖。关于其抗转移作用，土曲霉毒素显著抑制A549细胞的黏附、迁移和侵袭。此外，土曲霉毒素抑制A549细胞的血管生成过程，包括血管内皮生长因子（VEGF）分泌、毛细血管样管形成以及VEGF/VEGFR2相互作用。这些现象伴随着整合素、FAK及其下游介质（如PI3K、AKT、mTORC1和P70S6K）蛋白水平的降低。所有这些数据表明土曲霉毒素能够抑制人肺癌细胞中的所有主要转移过程，这对癌症治疗至关重要。
