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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 APCmin/+ 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 IRE1α and c-Jun N-terminal kinase (JNK) signal pathway through the formation of the IRE1α-TRAF2-ASK1 complex. Pristimerin exhibited apoptosis-inducing activities in HCT116 colon cancer xenografts and APCmin/+ 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. [ABSTRACT FROM AUTHOR]

Background: Gambogenic acid (GNA), an active component of Garcinia hanburyi Hook.f. (Clusiaceae) (common name gamboge), exerts anti-inflammatory and antitumor properties. However, the underlying mechanism of GNA in colorectal cancer (CRC) is still not well understood.Purpose: This study aimed to investigate the antitumor effects and mechanisms of GNA on CRC in vitro and in vivo.Methods: Cell viability, colony formation and cell apoptosis assays were performed to determine the antitumor effects of GNA. qRT-PCR and Western blotting were performed to evaluate the expression of genes or proteins affected by GNA in vitro and in vivo. HCT116 colon cancer xenografts and the APCmin/+ mice model were used to confirm the antitumor effects of GNA on CRC in vivo.Results: GNA induced Noxa-mediated apoptosis by inducing reactive oxygen species (ROS) generation and c-Jun N-terminal kinase (JNK) activation. Moreover, GNA triggered endoplasmic reticulum (ER) stress, which subsequently activated inositol-requiring enzyme-1α (IRE1α) leading to JNK phosphorylation. ROS scavenger attenuated GNA-induced IRE1α activation and JNK phosphorylation. Knockdown of IRE1α also prevented GNA-induced JNK phosphorylation. In vivo, GNA suppressed tumor growth and progression in HCT116 colon cancer xenografts and the APCmin/+ mices model.Conclusion: These findings revealed that GNA induced Noxa-mediated apoptosis by activating the ROS/IRE1α/JNK signaling pathway in CRC both in vitro and in vivo. GNA is therefore a promising antitumor agent for CRC treatment. [ABSTRACT FROM AUTHOR]

The excessive release of proinflammatory chemokines promotes cell proliferation and tumor growth in colorectal cancer. However, their regulatory functions and molecular pathogenesis have not been well elucidated. Here, we observed the upregulation of chemokine (C-X-C motif) ligand 13 (CXCL13) in human colorectal cancers and mouse intestinal tumors. Both CXCL13 deficiency and blockade of CXCL13 signaling ameliorated disease progression. CXCL13 promoted intestinal tumorigenesis through the activation of the AKT signaling pathway in a C-X-C chemokine receptor type 5 (CXCR5)-dependent manner. Intestinal microbiota translocation drove CXCL13 production in dendritic cells through the activation of NF-κB signaling. Inhibition of microbiota translocation decreased CXCL13 production and ameliorated intestinal tumorigenesis. Together, the results of this study identify a role for the CXCL13-CXCR5 axis is involved in the crosstalk between chemokines and cell growth during the development of intestinal tumorigenesis, which also provides a therapeutic strategy for targeting CXCL13/CXCR5 in the future clinical treatment of intestinal tumors. [ABSTRACT FROM AUTHOR]