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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01341

Synthesis of Chalcone Derivatives: Inducing Apoptosis of HepG2 Cells via regulating ROS and Mitochondrial Pathways

 Hongtian Zhu1, Lei Tang1, Chenghong Zhang1, Dian He1*,  Lifang Zheng1* and Baochu Wei1
  • 1Lanzhou University, China

Chalcone derivatives, as a hot research field, display a wide range of physiological activities and target a variety of biological receptors. Based on the parental structure of (E)-1,3-diphenyl-2-propene-1-one, 14 chalcone derivatives were designed and synthesized for the first time, and tested as the antitumor agents against four human cancer cell lines (A549, Hela, HepG2, and HL-60) and one normal cell line (WI-38). The most potent compound a14 displayed significant anti-hepatoma activity with IC50 of 38.33 μM and relatively weak cytotoxicity with IC50 of 121.29 μM in normal cells WI-38. In addition, compound a14 could effectively block the cell division of HepG2 cell lines in G2/M phase and robustly induced generation of ROS, and the application of the ROS scavenger N-acetylcysteine (NAC) could completely counteract the HepG2 cells death triggered by a14, which demonstrated that the generation of ROS induced by a14 was a main reason resulting in the apoptosis of HepG2 cells. Moreover, the mitochondrial membrane potential (MMP) of HepG2 cells treated with a14 was significantly decreased, which was closely related to ROS level. Furthermore, based on the Western blot experiment, cell apoptosis induced by a14 also involved the expression of Bcl-2 family and Caspase 3 protein. In summary, compound a14 could contribute the apoptosis of HepG2 cells via regulating ROS--mitochondrial pathway, which provide valuable hints for the discovery of novel anti-tumor drug candidates.

Keywords: Chalcone, HepG2 cell, ROS, mitochondrial membrane potential, Bcl-2, Caspase 3

Received: 02 Jul 2019; Accepted: 22 Oct 2019.

Copyright: © 2019 Zhu, Tang, Zhang, He, Zheng and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Dian He, Lanzhou University, Lanzhou, China, Hed@lzu.edu.cn
Dr. Lifang Zheng, Lanzhou University, Lanzhou, China, zhenglf@lzu.edu.cn