Rachmi Eva, Purnomo Basuki Bambang, Endharti Agustina Tri, Fitri Loeki Enggar
Department of Anatomy, Medical Faculty, Universitas Mulawarman, Samarinda.
Department of Urology, Medical Faculty, Universitas Brawijaya/dr. Saiful Anwar General Hospital.
Porto Biomed J. 2020 Nov 24;5(6):e095. doi: 10.1097/j.pbj.0000000000000095. eCollection 2020 Nov-Dec.
Triple-negative breast cancer (TNBC) tends to be aggressive and metastatic, characteristics attributable to its cellular migration capabilities. Afzelin is a chemical compound with anti-metastatic potentials. This study aimed to predict proteins involved in TNBC cell migration which could be inhibited by afzelin.
The protein database was constructed from the Kyoto Encyclopedia of Genes and Genomes pathways collection which related to cell motility, then screened for druggability using SuperTarget and Therapeutic Target Database. The involvement of druggable proteins in the TNBC metastasis process was investigated through existing publications in The National Center for Biotechnology Information PubMed database. Inhibitory potential of afzelin toward target proteins was compared to the proteins' known-inhibitor, using the reverse docking method.
Ten proteins identified as potential targets of afzelin, with the top 3 being ERK2, KRas, and FAK, respectively. Afzelin's 3-O-rhamnoside group played a dominant role in forming hydrogen bonds with the target proteins. Further analysis with STRING suggested that afzelin might be able to inhibit chemotaxis and haptotaxis of TNBC cells.
Afzelin was predicted to inhibit TNBC cell motility, by targeting ERK2, KRas, and FAK activation.
三阴性乳腺癌（TNBC）往往具有侵袭性和转移性，这些特征归因于其细胞迁移能力。阿夫泽林是一种具有抗转移潜力的化合物。本研究旨在预测参与TNBC细胞迁移且可被阿夫泽林抑制的蛋白质。
蛋白质数据库由与细胞运动相关的京都基因与基因组百科全书通路集合构建而成，然后使用SuperTarget和治疗靶点数据库筛选其成药可能性。通过美国国立生物技术信息中心PubMed数据库中的现有出版物研究可成药蛋白质在TNBC转移过程中的参与情况。使用反向对接方法将阿夫泽林对靶蛋白的抑制潜力与蛋白质的已知抑制剂进行比较。
鉴定出10种蛋白质为阿夫泽林的潜在靶点，其中排名前三的分别是ERK2、KRas和FAK。阿夫泽林的3 - O - 鼠李糖苷基团在与靶蛋白形成氢键中起主导作用。STRING的进一步分析表明，阿夫泽林可能能够抑制TNBC细胞的趋化性和趋触性。
预计阿夫泽林通过靶向ERK2、KRas和FAK的激活来抑制TNBC细胞的运动。
