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Pterostilbene Inhibits Adipocyte Conditioned-Medium-Induced Colorectal Cancer Cell Migration through Targeting
Yu-Hsuan Hsiao1, Nien-Chi Chen1, Yen-Chun Koh1
1Institute of Food Sciences and Technology , National Taiwan University , No. 1, Sec. 4, Roosevelt Road , Taipei 106 , Taiwan.
Abstract:
Pterostilbene (PTS) is a phenolic compound with diverse pharmacologic activities. However, its potential for inhibiting obesity-related colorectal cancer (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 prometastatic factors such as vascular endothelial growth factor, matrix metalloproteinase-2 (MMP2), MMP9, and extracellular tumor necrosis factor 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), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases 1/2 (JNK 1/2) signaling pathways activation that are upstream of NF-κB, β-catenin, and PPAR-γ. Therefore, we suggest that PTS could alleviate adiposity-induced metastasis in CRC via inhibiting cell migration through downregulating FABP5 gene expression.
Insights
Pterostilbene (PTS) inhibits colorectal cancer (CRC) metastasis by downregulating fatty acid-binding protein 5 (FABP5) and key signaling pathways. This phenolic compound offers potential for managing obesity-related CRC progression.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Obesity is a risk factor for colorectal cancer (CRC) progression and metastasis.
- Pterostilbene (PTS), a phenolic compound, exhibits various pharmacological activities but its role in obesity-related CRC is not well understood.
Purpose of the Study:
- To investigate the mechanism by which PTS inhibits adipocyte-conditioned medium (aCM)-induced malignant transformation and metastasis in HT-29 colorectal adenocarcinoma cells.
Main Methods:
- Cells were treated with aCM and PTS.
- Expression of FABP5, prometastatic factors (VEGF, MMP2, MMP9, TNFα), and signaling pathway proteins (NF-κB, β-catenin, PPAR-γ, PI3K/Akt, MAPK/ERK, JNK) were analyzed.
Main Results:
- PTS downregulated aCM-induced FABP5 and prometastatic factors (VEGF, MMP2, MMP9, TNFα).
- PTS inhibited activation of NF-κB, β-catenin, and PPAR-γ pathways.
- PTS suppressed upstream signaling pathways including PI3K/Akt, p38 MAPK, ERK, and JNK 1/2.
Conclusions:
- Pterostilbene exhibits anti-metastatic properties in colorectal cancer by inhibiting FABP5 expression and multiple oncogenic signaling pathways.
- PTS may serve as a potential therapeutic agent to counteract obesity-induced CRC metastasis.
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