1. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibits tumor growth via suppression of NF-κB and induction of death receptor 6.
- Author
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Ban JO, Jung YS, Kim DH, Park KR, Yun HM, Lee NJ, Lee HP, Shim JH, Jeong HS, Lee YH, Ham YW, Han SB, and Hong JT
- Subjects
- Aldehydes chemistry, Animals, Apoptosis drug effects, Cell Line, Tumor, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms physiopathology, Down-Regulation drug effects, Humans, I-kappa B Kinase chemistry, I-kappa B Kinase genetics, I-kappa B Kinase metabolism, Male, Mice, Inbred BALB C, Molecular Docking Simulation, NF-kappa B genetics, Phenols chemistry, Protein Structure, Tertiary, Receptors, Tumor Necrosis Factor genetics, Aldehydes administration & dosage, Cell Proliferation drug effects, Colonic Neoplasms drug therapy, NF-kappa B metabolism, Phenols administration & dosage, Receptors, Tumor Necrosis Factor metabolism
- Abstract
The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on in vitro and in vivo colon cancer. We analysed the anti-cancer activity of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it's mechanism, NF-κB DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-κB activity. In docking model as well as pull-down assay, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKKβ, thereby inhibited IKKβ activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKKβ/NF-κB activity, and overexpression of DR6. These results suggest that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKKβ/NF-κB activity and induction of DR6 expression.
- Published
- 2014
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