Pterostilbene inhibits adipocyte conditioned-medium-induced colorectal cancer cell migration through targeting FABP5-related signaling pathway.
J Agric Food Chem. 2019 Aug 16. Epub 2019 Aug 16. PMID: 31419115
Pterostilbene (PTS) is a phenolic compound with diverse pharmacologic activities. However, its potential for inhibiting obesity-related CRC remains unclear. Our study evaluated the mechanism of inhibitory effects of PTS on adipocyte conditioned-medium (aCM)-induced malignant transformation in HT-29 colorectal adenocarcinoma cells. The results demonstrated that PTS could downregulate the expression of aCM-induced fatty acid-binding protein 5 (FABP5) and pro-metastasis factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2), MMP9, and extracellular tumor necrosis factor alpha (TNF-α) via inhibiting aCM-induced nuclear factor-kappa B (NF-κB), β-catenin, and peroxisome proliferator-activated receptor γ (PPAR-γ). Moreover, PTS can suppress aCM-stimulated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellularsignal-regulated kinase (ERK), and c-Jun N-terminal kinases 1/2 (JNK 1/2) signaling pathways activation that are upstream of NF-B, β-catenin, and PPAR-γ. Therefore, we suggest that PTS could alleviate adiposity-induced cachexia in CRC via inhibiting cell migration through downregulating FABP5 gene expression.