Molecular simulation and experimental study on role of BRAF in anti-melanoma effect of 10-gingerol |
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| Authors: | ZHANG Jing-zhi DENG Bo JIANG Xiao-li ZHANG Shuang-wei CAI Min LIU Bin |
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| Institution: | 1. Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China;
2. Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China;
3. HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518057, China |
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| Abstract: | AIM:To investigate the role of BRAF protein in the anti-melanoma effect of 10-gingerol (10-G) by molecular simulation techniques and cell experiments. METHODS:Human skin melanoma A375 cells were induced by 10-G (10, 20 and 40 μmol/L) for 24 h. The cell viability was measured by MTS assay and cell counting. The interaction between 10-G and BRAF protein was analyzed by molecular docking and molecular dynamics simulations. The protein levels of p-BRAF, BRAF, p-MEK1/2, p-ERK1/2 and p-P38 were determined by Western blot. RESULTS:Treatment with 10-G significantly reduced the cell viability and cell number in a dose-dependent manner (P<0.01). The binding energy between 10-G and wild-type BRAF was -7.358 kcal/mol, and that between 10-G and V600E mutant BRAF (BRAFV600E) was -8.255 kcal/mol. Molecular dynamics simulations confirmed that the binding between BRAFV600E and 10-G was stable. The protein levels of p-BRAF, p-MEK1/2 and p-P38 in the A375 cells was significantly reduced by 10-G (P<0.01), while the protein level of p-ERK1/2 was unchanged. CONCLUSION:The viability of melanoma cells is significantly inhibited by 10-G. The mechanism might be related to the inhibition of BRAF activation. |
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| Keywords: | 10-Gingerol Melanoma Cell viability BRAF protein Molecular simulations |
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