%0 Journal Article
%T Evidence that TNF
%A Ajay Goel
%A Bastian Popper
%A Bharat B Aggarwal
%A Constanze Buhrmann
%A Mehdi Shakibaei
%A Mina Yazdi
%A Parviz Shayan
%J Experimental Biology and Medicine
%@ 1535-3699
%D 2019
%R 10.1177/1535370218824538
%X Although much is understood about the proinflammatory cytokine TNF-汐, very limited data are available about TNF-汕 (lymphotoxin). Whether TNF-汕 can induce the proliferation of tumor cells, how TNF-汕-induced proliferation of tumor cells is affected by natural products such as resveratrol and the role of NF-百B in this process, is not understood. In the present study, we used clonogenic and cytotoxic methods to show the effect of TNF-汕 on cell proliferation. We also examined the impact of resveratrol on TNF-汕-promoted proliferation and on NF-百B activation in HCT116 colorectal cancer (CRC). Our findings showed that TNF-汕 induced the proliferation and invasion in CRC cells and this was comparable with that of TNF-汐. TNF-汕-stimulated proliferation of CRC cells was blocked via anti-TNF-汕-receptor. We found that resveratrol reversed the TNF-汕-induced proliferation and invasion of CRC cells, and this correlated with the suppression of TNF-汕-stimulated NF-百B signaling. Like resveratrol, I百B-kinase (IKK) inhibitor (BMS-345541), also reversed TNF-汕-stimulated proliferation, NF-百B activation and these were mediated through inhibition of I百B-kinase, phosphorylation of I百B汐, suppression of phosphorylation, and nuclear translocation of the p65 subunit of NF-百B. Furthermore, resveratrol similar to BMS-345541 suppressed TNF-汕-promoted NF-百B-mediated gene biomarkers linked with proliferation, apoptosis, and invasion. Overall, our findings indicate for the first time that TNF-汕/TNF-汕-receptor signaling is involved in proliferation of CRC cells in parallel to TNF-汐, and that resveratrol down-modulates TNF-汕/TNF-汕-receptor-mediated inflammatory response, at least in part through down modulating NF-百B activation, thereby regulating tumor cell growth. The mechanism by which natural products such as resveratrol suppresses TNF-汕-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-汕-, compared to TNF-汐-stimulated proliferative and pro-inflammatory signaling in HCT116 cells. Our findings suggest that expression of TNF-汕 and TNF-汕-receptor, like TNF-汐, can lead to activation of inflammatory transcription factor (NF-百B) and NF-百B-regulated gene biomarkers, which are involved in the promotion of cancer proliferation, invasion, metastasis, and cell survival of tumor. Resveratrol can block TNF-汕/TNF-汕-receptor-induced activation of NF-百B, NF-百B-modulated gene products, and inhibition of caspase-3 cleavage. These results highlight the therapeutic effect of
%K Resveratrol
%K colorectal cancer
%K TNF-汕
%K NF-百B
%K proliferation
%U https://journals.sagepub.com/doi/full/10.1177/1535370218824538