Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway
AbstractMalignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma. View Full-Text
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Peng, K.-T.; Chiang, Y.-C.; Ko, H.-H.; Chi, P.-L.; Tsai, C.-L.; Ko, M.-I.; Lee, M.-H.; Hsu, L.-F.; Lee, C.-W. Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway. Int. J. Mol. Sci. 2018, 19, 2649.
Peng K-T, Chiang Y-C, Ko H-H, Chi P-L, Tsai C-L, Ko M-I, Lee M-H, Hsu L-F, Lee C-W. Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway. International Journal of Molecular Sciences. 2018; 19(9):2649.Chicago/Turabian Style
Peng, Kuo-Ti; Chiang, Yao-Chang; Ko, Horng-Huey; Chi, Pei-Ling; Tsai, Chia-Lan; Ko, Ming-I; Lee, Ming-Hsueh; Hsu, Lee-Fen; Lee, Chiang-Wen. 2018. "Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway." Int. J. Mol. Sci. 19, no. 9: 2649.
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