Mehmet Berköz1, Ferbal Özkan-Yılmaz2, Arzu Özlüer-Hunt3, Mirosław Krośniak4, Ömer Türkmen5, Duygu Korkmaz6, Sıddık Keskin7. 1. Department of Biochemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Zeve Campus, 65080, Van, Turkey. mehmetberkoz@yyu.edu.tr. 2. Department of Basic Sciences, Faculty of Fisheries, Mersin University, 33160, Mersin, Turkey. 3. Department of Aquaculture, Faculty of Fisheries, Mersin University, 33160, Mersin, Turkey. 4. Department of Food Chemistry and Nutrition, Medical College, Jagiellonian University, 9 Medyczna St., Kraków, 30-688, Poland. 5. Department of Pharmaceutical Technology, Faculty of Pharmacy, Van Yuzuncu Yil University, Van, 65080, Turkey. 6. Department of Medical Education, Faculty of Medicine, Van Yuzuncu Yil University, Van, 65080, Turkey. 7. Department of Biostatistics, Faculty of Medicine, Van Yuzuncu Yil University, Van, 65080, Turkey.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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 A375humanmelanoma cell line. METHODS: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. RESULTS: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. CONCLUSION: 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.
Authors: A Raffetin; F Bruneel; C Roussel; M Thellier; P Buffet; E Caumes; S Jauréguiberry Journal: Med Mal Infect Date: 2018-02-13 Impact factor: 2.152
Authors: Anne Hamacher-Brady; Henning A Stein; Simon Turschner; Ina Toegel; Rodrigo Mora; Nina Jennewein; Thomas Efferth; Roland Eils; Nathan R Brady Journal: J Biol Chem Date: 2010-12-13 Impact factor: 5.157