Sesquiterpene binding Gly-Leu-Ser/Lys-"co-adaptation pocket" to inhibit lung cancer cell epithelial-mesenchymal transition

倍半萜结合Gly-Leu-Ser/Lys-“共适应口袋”抑制肺癌细胞上皮-间质转化

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作者:Xiao-Yu Ai, Heng Zhang, Shao-Yan Gao, Yuan Qin, Wei-Long Zhong, Ju Gu, Meng Li, Kai-Liang Qiao, Qin Tian, Zhan-Hong Cui, Jia-Huan Yang, Zhun Bi, Ting Xiao, Shuang Chen, Hui-Juan Liu, Hong-Gang Zhou, Tao Sun, Cheng Yang

Abstract

Sesquiterpene lactones (SL) have a wide range of applications in anti-tumor and anti-inflammatory therapy. However, the pharmacological mechanism of such substances is not clear. In this study, parthenolide (PTL) was used as an example to explore the anti-tumor effect of natural molecules and their common mechanism. We showed that PTL inhibited the proliferation and migration by reverse EMT via the ERK2/NF-κB/Snail pathway in vivo and in vitro. Interestingly, Multiple potential targets of PTL contain a Gly-Leu-Ser/Lys-"co-adaptation pocket". This inspiring us analogies of PTL may also bind to these target proteins and play a similar function. Significantly, the Concept of co-adaptation pocket may help to increase the selectivity of drug research and development.

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