CFNC, a neocryptolepine derivative, inhibited the growth of gastric cancer AGS cells by inhibiting PI3K/AKT signaling pathway

• DOI: 10.1016/j.ejphar.2022.175408
• Publication Date: 2022-11-25T19:51:07Z
• Authors: Yunhao Ma; Hao Xu; Zhongkun Zhou; Yanan Tian; Kangjia Du; Hao Zhang; Xinrong Jiang; Juan Lu; Yuqing Niu; Lixue Tu; Huanxiang Liu; Hongmei Zhu; Peng Chen; Yingqian Liu
• Keywords: 0301 basic medicine; Biological Products; TOR Serine-Threonine Kinases; Apoptosis; Antineoplastic Agents; 3. Good health; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Stomach Neoplasms; Cell Line, Tumor; Humans; Proto-Oncogene Proteins c-akt; Signal Transduction; Cell Proliferation

Gastric cancer is highly heterogeneous and there is still a lack of efficient, low-toxicity small molecule compounds for the treatment of gastric cancer. Natural products are important sources for the development of antitumor compounds. Therefore, it is promising strategy to find the lead compound of anti-gastric cancer agents by structural modification of natural products. The aim of this study was to synthesize a novel neocryptolepine derivative CFNC and explore its potential anti-gastric cancer effect and molecular mechanism. The MTT assay showed that the IC50 of CFNC on AGS cells reached 148 nM. CFNC arrested AGS cells in the G2/M phase of the cell cycle. Furthermore, CFNC inhibited cell proliferation and migration, leading to the loss of membrane potential by causing mitochondrial dysfunction, which induced the apoptosis of AGS cells. Western blot assay suggested that CFNC could inhibit the expression of important proteins in the PI3K/AKT/mTOR signaling pathway. These results showed that CFNC exhibited strong cytotoxic activity in gastric cancer cell lines by regulating the PI3K/AKT/mTOR signaling pathway. Taken together, CFNC could be a promising lead compound for the clinical treatment of gastric cancer.