Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042, Belgrade, Serbia.
Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042, Belgrade, Serbia.
J Cancer Res Clin Oncol. 2023 Oct;149(13):10975-10987. doi: 10.1007/s00432-023-04930-9. Epub 2023 Jun 4.
Sarcomas are rare and heterogenic tumors with unclear etiology. They develop in bone and connective tissue, mainly in pediatric patients. To increase efficacy of current therapeutic options, natural products showing selective toxicity to tumor cells are extensively investigated. Here, we evaluated antitumor activity of bacterial pigment violacein in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines.
The toxicity of violacein was assessed in vitro and in vivo, using MTT assay and FET test. The effect of violacein on cell migration was monitored by wound healing assay, cell death by flow cytometry, uptake of violacein by fluorescence microscopy, generation of reactive oxygen species (ROS) by DCFH-DA assay and lipid peroxidation by TBARS assay.
Violacein IC values for OS and RMS cells were in a range from 0.35 to 0.88 µM. Its selectivity toward malignant phenotype was confirmed on non-cancer V79-4 cells, and it was safe in vivo, for zebrafish embryos in doses up to 1 µM. Violacein induced apoptosis and affected the migratory potential of OS and RMS cells. It was found on the surfaces of tested cells. Regarding the mechanism of action, violacein acted on OS and RMS cells independently of oxidative signaling, as judged by no increase in intracellular ROS generation and no lipid peroxidation.
Our study provided further evidence that reinforces the potential of violacein as an anticancer agent and candidate to consider for improvement of the effectiveness of traditional OS and RMS therapies.
肉瘤是一种罕见且具有异质性的肿瘤，其病因尚不清楚。它们发生在骨骼和结缔组织中，主要发生在儿科患者中。为了提高当前治疗选择的疗效，广泛研究了对肿瘤细胞具有选择性毒性的天然产物。在这里，我们评估了细菌色素表飞鸣在骨肉瘤（OS）和横纹肌肉瘤（RMS）细胞系中的抗肿瘤活性。
使用 MTT 测定法和 FET 试验在体外和体内评估表飞鸣的毒性。通过划痕愈合试验监测表飞鸣对细胞迁移的影响，通过流式细胞术检测细胞死亡，通过荧光显微镜观察表飞鸣的摄取，通过 DCFH-DA 测定法测定活性氧（ROS）的产生和通过 TBARS 测定法测定脂质过氧化。
OS 和 RMS 细胞的表飞鸣 IC 值范围为 0.35 至 0.88 µM。在非癌细胞 V79-4 细胞上证实了其对恶性表型的选择性，并且在高达 1 µM 的剂量下在斑马鱼胚胎中是安全的。表飞鸣诱导 OS 和 RMS 细胞凋亡并影响其迁移能力。它被发现在测试细胞的表面。关于作用机制，表飞鸣独立于氧化信号作用于 OS 和 RMS 细胞，因为没有增加细胞内 ROS 的产生，也没有脂质过氧化。
我们的研究进一步证明了表飞鸣作为一种抗癌剂的潜力，并为提高传统 OS 和 RMS 治疗的有效性提供了候选药物。
