Effect of pristimerin on apoptosis through activation of ROS/ endoplasmic reticulum (ER) stress-mediated noxa in colorectal cancer

Background: Pristimerin, a natural quinonemethid triterpenoid found in different spp. of Celastraceae and Hippocrateaceae families, has been reported to exhibit potent antitumor activities against colorectal cancer (CRC). However, the mechanisms underlying pristimerin-induced apoptosis in CRC is not clear. Purpose: This study aimed to investigate the mechanisms of pristimerin-induced apoptosis against CRC in vitro and in vivo. Methods: Cell viability and cell apoptosis analyses were conducted to assess the effects of pristimerin on CRC. Western blotting was performed to detect the expression of proteins affected by pristimerin in vitro and in vivo. HCT116 colon cancer xenografts and APC(min/+) mouse models were used to evaluate the anti-CRC effect of pristimerin in vivo. Results: Our data showed that pristimerin induced apoptosis by regulating proapoptotic proteins of which Noxa showed higher expression. Pristimerin triggered reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress signaling activation. Pristimerin significantly elevated the expression of ER stress-related proteins, resulting in activation of the IRE1 alpha and c-Jun N-terminal kinase (JNK) signal pathway through the formation of the IRE1 alpha-TRAF2-ASK1 complex. Pristimerin exhibited apoptosis-inducing activities in HCT116 colon cancer xenografts and APC(min/+) mice. Conclusion: Both in vitro and in vivo data demonstrated that pristimerin induced Noxa expression and apoptosis through activation of the ROS/ER stress/JNK axis in CRC. Thus, pristimerin may be a promising antitumor agent for CRC.

Automated summary

Pristimerin induces apoptosis in CRC cells by regulating proapoptotic protein Noxa and triggering ROS-mediated ER stress signaling activation. Pristimerin significantly elevates ER stress-related proteins expression, leading to activation of the IRE1 alpha/JNK signal pathway. Pristimerin exhibits apoptosis-inducing activities in both HCT116 colon cancer xenografts and APC(min/+) mice.