Evidence that TNF-β induces proliferation in colorectal cancer cells and resveratrol can down-modulate it.

IMPACT STATEMENT: The mechanism by which natural products such as resveratrol suppresses TNF-β-promoted tumor cell proliferation, invasion, and colony formation is unknown. In this study, we explored for the first time the effect of resveratrol on the proinflammatory cytokine TNF-β-, compared to TNF-α-stimulated proliferative and pro-inflammatory signaling in HCT116 cells. Our findings suggest that expression of TNF-β and TNF-β-receptor, like TNF-α, can lead to activation of inflammatory transcription factor (NF-κB) and NF-κB-regulated gene biomarkers, which are involved in the promotion of cancer proliferation, invasion, metastasis, and cell survival of tumor. Resveratrol can block TNF-β/TNF-β-receptor-induced activation of NF-κB, NF-κB-modulated gene products, and inhibition of caspase-3 cleavage. These results highlight the therapeutic effect of resveratrol-mediated anti-tumor activity by multitargeting cellular signaling pathways.