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

// Xiao-Yu Ai 1, * , Heng Zhang 1, * , Shao-Yan Gao 1, * , Yuan Qin 1, 2 , Wei-Long Zhong 1, 2 , Ju Gu 1, 2 , Meng Li 1, 2 , Kai-Liang Qiao 1, 2 , Qin Tian 1, 2 , Zhan-Hong Cui 1, 2 , Jia-Huan Yang 1, 2 , Zhun Bi 1 , Ting Xiao 1, 2 , Shuang Chen 2 , Hui-Juan Liu 2 , Hong-Gang Zhou 1, 2 , Tao Sun 1, 2 and Cheng Yang 1, 2 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China 2 Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China * These authors have contributed equally to this work Correspondence to: Cheng Yang, email: Cheng.yang@nankai.edu.cn Tao Sun, email: sunrockmia@hotmail.com Hong-Gang Zhou, email: honggang.zhou@vip.126.com Keywords: antitumor, EMT, co-adaptation pocket, ERK2, lung cancer Abbreviations: SL: sesquiterpene lactones; PTL: parthenolide; EMT: epithelial–mesenchymal transition Received: March 15, 2017      Accepted: June 20, 2017      Published: July 26, 2017 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.