Asian Journal of Complementary and Alternative Medicine
E-mail: editor@acamjournal.com
Centipede Polypeptide Affects the Inflammatory Reaction and Ferroptosis of Liver Cancer Cells Through the p53/TRAIL Pathway
Xingru Xing1, Linzhu Lu1#, Zhen Huang1, Zhuang Kang1, Jiawei Wang1, Lihuai Wang3, Yuxing Hu4, Xuefei Tian1 , Xingxing Fan2 and Sha Tian1,2*
1Department of Internal Medicine, College of Integrated Chinese and Western Medicine of Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
2State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China
3The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
Abstract
Background: Various extracts from centipedes have therapeutic effects on liver cancer. This study aims to illustrate the effect and mechanism of centipede polypeptide (CP) on liver cancer.
Methods: The suitable CP concentration and liver cancer cells were screened through CCK-8 analysis. The expression of proteins was analyzed by Western blot. The level of cytokines and markers was measured by ELISA and biochemical kits. The apoptosis rate of cells was analyzed by TUNEL staining and flow cytometry. Histopathological changes were observed by HE staining. The expression of ki67 and Caspase-3 was assessed by IHC staining. The combination of CP and p53 was simulated by molecular docking.
Results: 200 μg/mL CP and HepG2 cells were applied in experiments. CP up-regulated the expressions of p53, TRAIL, TRADD, and TRAF in HepG2 cells and tumor tissues (P<0.05). CP raised the levels of IL-6, IL-1β, TNF-α, MDA, and ROS, and decreased that of IL-10, TGF-β1, and SOD in HepG2 cell supernatant and serum of nude mice (P<0.05). CP promoted cell apoptosis and reduced the levels of ALT and AST to inhibit the progression of cancer. Molecular docking showed that CP could bind stably to p53 (P<0.05). Silencing of p53 restrained the activation of the p53/TRAIL pathway, and reduced the level of inflammatory reaction and ferroptosis, thus reversing the therapeutic effect of CP on liver cancer (P<0.05).
Conclusion: CP affected the inflammatory reaction and ferroptosis of liver cancer cells through the p53/TRAIL pathway.