Department of Biochemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Zeve Campus, 65080, Van, Turkey.
Department of Basic Sciences, Faculty of Fisheries, Mersin University, 33160, Mersin, Turkey.
Pharmacol Rep. 2021 Apr;73(2):650-663. doi: 10.1007/s43440-021-00230-6. Epub 2021 Feb 20.
Melanoma is a life-threatening cancer characterized with a potentially metastatic tumor of melanocytic origin. Improved methods or novel therapies are urgently needed to eliminate the development of metastases. Artesunate is a semi-synthetic derivative of artemisinin used for trarment of malaria and cancer. The purpose of this study was to investigate the anti-cancer effect of artesunate and the role on STAT3 signaling in A375 human melanoma cell line.
Melanoma cells were treated with artesunate at concentrations of 0-5 μM for 24 and 48 h. The inhibition of cell viability, colony formation, migration, invasion, adhesion, percentage of apoptotic cells, and expressions of signal transducer and activator of transcription-3 (STAT3) and related proteins were examined.
Artesunate inhibited cellular proliferation of cancer cells by induction of apoptosis at sub-toxic doses. Cells treated with artesunate showed an inhibition in adhesion to extracellular matrix substrate matrigel and type IV collagen. Artesunate treatment showed a decreased cellular migration, invasion, and colony formation in melanoma cells. Artesunate also inhibited STAT3 and Src activations and STAT3 related protein expressions; such as metalloproteinase 2 (MMP-2), MMP-9, Mcl-1, Bxl-xL, vascular endothelial growth factor (VEGF), and Twist. Moreover, overexpression of constitutively active STAT3 in A375 cells attenuated the anti-proliferative, apoptotic and anti-invasive effects of artesunate.
The results obtained from this study demonstrated that the anticancer activity of artesunate occurred via STAT3 pathway and its target proteins. Therefore, it can be suggested that artesunate may be an important candidate molecule in the treatment of melanoma.
黑色素瘤是一种危及生命的癌症，其特征是具有潜在转移性的黑色素细胞来源的肿瘤。迫切需要改进方法或新的治疗方法来消除转移的发展。青蒿琥酯是青蒿素的半合成衍生物，用于治疗疟疾和癌症。本研究的目的是研究青蒿琥酯对 A375 人黑色素瘤细胞系的抗癌作用及其对 STAT3 信号通路的作用。
用青蒿琥酯在 0-5μM 浓度下处理黑色素瘤细胞 24 和 48 小时。检测细胞活力抑制、集落形成、迁移、侵袭、黏附、凋亡细胞百分比以及信号转导和转录激活因子 3（STAT3）和相关蛋白的表达。
青蒿琥酯在亚毒性剂量下通过诱导细胞凋亡抑制癌细胞的细胞增殖。用青蒿琥酯处理的细胞显示对细胞外基质基质胶和 IV 型胶原的黏附抑制。青蒿琥酯处理显示黑色素瘤细胞的细胞迁移、侵袭和集落形成减少。青蒿琥酯还抑制 STAT3 和 Src 的激活以及 STAT3 相关蛋白的表达，如基质金属蛋白酶 2（MMP-2）、MMP-9、Mcl-1、Bxl-xL、血管内皮生长因子（VEGF）和 Twist。此外，在 A375 细胞中过表达组成型激活的 STAT3 减弱了青蒿琥酯的抗增殖、凋亡和抗侵袭作用。
本研究结果表明，青蒿琥酯的抗癌活性通过 STAT3 通路及其靶蛋白发生。因此，可以认为青蒿琥酯可能是治疗黑色素瘤的重要候选分子。
