Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata 700 026, India.
Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
Int J Mol Sci. 2019 Jan 31;20(3):608. doi: 10.3390/ijms20030608.
Malignant melanoma is a highly aggressive form of skin cancer which has a propensity for metastasis. Epithelial mesenchymal transition (EMT) plays a primordial role in the progression of metastatic disease. Metastatic melanoma is resistant to conventional therapies. Hence, researchers have been exploring alternative approaches, including the utility of bioactive phytochemicals to manage metastatic disease. In the present study, we investigated the potential of cirsiliol, a flavonoid isolated from L., in modulating the aggressive behavior of B16F10 metastatic melanoma cells, including EMT, and associated molecular mechanisms of action. Cirsiliol was found to be effective in restraining the colony formation and migration of fibronectin-induced B16F10 metastatic melanoma cells. Cirsiliol inhibited the activity and expression of matrix metalloproteinase-9 (MMP-9). Cirsiliol also suppressed the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (also known as Akt)/nuclear factor-κB (NF-κB) signaling pathway which, in turn, caused upregulation of E-cadherin and downregulation of N-cadherin, Snail and Twist. Based on these results, cirsiliol may be considered a promising compound against EMT in the therapeutic management of malignant melanoma.
恶性黑色素瘤是一种具有转移倾向的高度侵袭性皮肤癌。上皮间质转化（EMT）在转移性疾病的进展中起着重要作用。转移性黑色素瘤对常规治疗具有耐药性。因此，研究人员一直在探索替代方法，包括利用生物活性植物化学物质来控制转移性疾病。在本研究中，我们研究了从 中分离得到的类黄酮化合物芹菜素在调节 B16F10 转移性黑色素瘤细胞侵袭行为，包括 EMT 及其相关作用机制中的潜在作用。研究发现，芹菜素能有效抑制纤维连接蛋白诱导的 B16F10 转移性黑色素瘤细胞的集落形成和迁移。芹菜素抑制基质金属蛋白酶-9（MMP-9）的活性和表达。芹菜素还抑制了磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶 B（也称为 Akt）/核因子-κB（NF-κB）信号通路，从而导致 E-钙黏蛋白上调和 N-钙黏蛋白、Snail 和 Twist 下调。基于这些结果，芹菜素可能被认为是一种有前途的化合物，可用于治疗恶性黑色素瘤的 EMT。
