2. Academic Validation
  3. A novel chalcone derivative S17 induces apoptosis through ROS dependent DR5 up-regulation in gastric cancer cells

A novel chalcone derivative S17 induces apoptosis through ROS dependent DR5 up-regulation in gastric cancer cells

  • Sci Rep. 2017 Aug 29;7(1):9873. doi: 10.1038/s41598-017-10400-3.
Saiyang Zhang 1 2,  Tingyu Li 1,  Li Zhang 1,  Xiangyu Wang 1,  Hangqi Dong 1,  Lili Li 1,  Dongjun Fu 1,  Yongchun Li 1,  Xiaolin Zi 3,  Hong-Min Liu 1,  Yanbing Zhang 1,  Hongde Xu 4,  Cheng-Yun Jin 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China.
  • 2 School of Basic Medicinal Science, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China.
  • 3 Departments of Urology, Pharmacology and Pharmaceutical Sciences, University of California, Irvine, Orange, USA.
  • 4 School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China. [email protected].
  • 5 School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China. [email protected].
PMID: 28852176 DOI: 10.1038/s41598-017-10400-3
Abstract

A new series of etherification chalcone derivatives were designed and synthesized through Willimison etherification and Claisen-Schmidt condensation. Among them, compound 2-c which was given chemical name of S17, has been successfully screened out as the most potent one on gastric Cancer cell line(MGC803) through the investigation for their effects against the growth of five Cancer cell lines (EC109, HepG2, MCF7, MGC803, SKNSH). S17 exhibited strong anti-proliferative activity on other two gastric Cancer cells (HGC27 and SGC7901), but less cytotoxicity to non-malignant gastric epithelial cells GES1. S17 potently killed gastric Cancer cells with causing modulation of Bcl-2 Family proteins and activation of Caspase 9/3 cascade. S17 also up-regulated DR5 expression and DR5 knockdown partially reversed S17-induced Apoptosis, Caspase activation and MMP decrease. S17 robustly induced generation of ROS with Keap/Nrf2 pathway activated and the application of ROS scavenger N-acetyl cysteine (NAC) completely blocked these effects by S17 in MGC803 cells. Intraperitoneal administration of S17 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that S17 is a leadbrominated chalcone derivate and deserves further investigation for prevention and treatment of gastric Cancer.

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