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Published on: February 10, 2023
Evidence that TNF-β induces proliferation in colorectal cancer cells and resveratrol can down-modulate it
Constanze Buhrmann1, Mina Yazdi1, Bastian Popper2
11 Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, Munich 80336, Germany.
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.
Insights
Resveratrol effectively inhibits tumor growth by blocking the TNF-β signaling pathway. This natural compound targets key cancer-promoting factors like NF-κB, offering therapeutic potential against various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Tumor necrosis factor-beta (TNF-β) promotes cancer proliferation, invasion, and survival.
- The precise mechanism of resveratrol's anti-tumor effects, particularly against TNF-β, remains unclear.
Purpose of the Study:
- To investigate resveratrol's impact on TNF-β-stimulated signaling in HCT116 cancer cells.
- To compare resveratrol's effects on TNF-β-induced pathways with those of TNF-α.
Main Methods:
- Utilized HCT116 cells to study TNF-β and TNF-α signaling pathways.
- Assessed the activation of nuclear factor-kappa B (NF-κB) and its downstream targets.
- Measured caspase-3 cleavage to evaluate apoptosis induction.
Main Results:
- TNF-β, similar to TNF-α, activates NF-κB and related genes, promoting cancer progression.
- Resveratrol effectively blocks TNF-β/TNF-β-receptor-induced NF-κB activation.
- Resveratrol inhibits NF-κB-modulated gene products and promotes caspase-3 cleavage, indicating apoptosis.
Conclusions:
- Resveratrol demonstrates significant anti-tumor activity by targeting multiple cellular signaling pathways.
- Blocking the TNF-β/NF-κB axis is a key mechanism for resveratrol's therapeutic effects.
- Resveratrol holds promise as a multi-targeting agent for cancer therapy.
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