Effect of pristimerin on apoptosis through activation of ROS/ endoplasmic reticulum (ER) stress-mediated noxa in colorectal cancer.
Abstract
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. This study aimed to investigate the mechanisms of pristimerin-induced apoptosis against CRC in vitro and in vivo. 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 APCmin/+ mouse models were used to evaluate the anti-CRC effect of pristimerin in vivo. 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 IRE1α and c-Jun N-terminal kinase (JNK) signal pathway through the formation of the IRE1α-TRAF2-ASK1 complex. Pristimerin exhibited apoptosis...Continue Reading
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Modulation of NOXA and MCL-1 as a strategy for sensitizing melanoma cells to the BH3-mimetic ABT-737
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis