TY - JOUR
T1 - Garcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway
AU - Li, Renkai
AU - Zheng, Chengwen
AU - Shiu, Polly Ho Ting
AU - Rangsinth, Panthakarn
AU - Wang, Wen
AU - Kwan, Yiu Wa
AU - Wong, Emily Sze Wan
AU - Zhang, Yanbo
AU - Li, Jingjing
AU - Leung, George Pak Heng
N1 - Publisher Copyright:
© 2023
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Colorectal cancer
KW - Reactive oxygen species
KW - Xanthone
UR - http://www.scopus.com/inward/record.url?scp=85151273704&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2023.114617
DO - 10.1016/j.biopha.2023.114617
M3 - Article
C2 - 37001180
AN - SCOPUS:85151273704
SN - 0753-3322
VL - 162
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 114617
ER -