Garcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway

Renkai Li, Chengwen Zheng, Polly Ho Ting Shiu, Panthakarn Rangsinth, Wen Wang, Yiu Wa Kwan, Emily Sze Wan Wong, Yanbo Zhang, Jingjing Li, George Pak Heng Leung

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Despite various therapeutic approaches, colorectal cancer is among the most fatal diseases globally. Hence, developing novel and more effective methods for colorectal cancer treatment is essential. Recently, reactive oxygen species (ROS)/JNK signaling pathway has been proposed as the potential target for the anticancer drug discovery. The present study investigated the anticancer effects of the bioactive xanthone garcinone E (GAR E) in mangosteen and explored its underlying mechanism of action. HT-29 and Caco-2 cancer cells were used as in vitro models to study the anticancer effect of GAR E. The findings demonstrated that GAR E inhibited colony formation and wound healing, whereas triggered the production of ROS, which induced mitochondrial dysfunction and apoptosis, causing cell cycle arrest at the Sub G1 phase. Additionally, GAR E treatment elevated the ratio of Bax/Bcl-2 and activated PARP, caspases 3 and 9, and JNK1/2. These GAR E-induced cytotoxic activities and expression of signaling proteins were reversed by the antioxidant N-acetyl-L-cysteine and JNK inhibitor SP600125, indicating the involvement of ROS/JNK signaling pathways. In vivo experiments using an HT-29 xenograft nude mouse model also demonstrated the antitumor effect of GAR E. In conclusion, our findings showed that GAR E might be potentially effective in treating colorectal cancer and provided insights into the development of xanthones as novel chemotherapeutic agents.

Original languageEnglish
Article number114617
JournalBiomedicine and Pharmacotherapy
Volume162
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Apoptosis
  • Colorectal cancer
  • Reactive oxygen species
  • Xanthone

Fingerprint

Dive into the research topics of 'Garcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway'. Together they form a unique fingerprint.

Cite this