(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibits tumor growth via suppression of NF-jB and induction of death receptor 6

Jung Ok Ban, Young Suk Jung, Dae Hwan Kim, Kyung Ran Park, Hyung Mun Yun, Nam Jin Lee, Hee Pom Lee, Jeong Hyun Shim, Heon Sang Jeong, Yun Hee Lee, Young Wan Ham, Sang Bae Han, Jin Tae Hong

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13 Citations (Scopus)

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-jB 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(phydroxyphenyl)- 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-jB 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 IKKb, thereby inhibited IKKb 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 IKKb/NF-jB 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 IKKb/NF-jB activity and induction of DR6 expression.

Original languageEnglish
Pages (from-to)165-178
Number of pages14
JournalApoptosis
Volume19
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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    Ban, J. O., Jung, Y. S., Kim, D. H., Park, K. R., Yun, H. M., Lee, N. J., Lee, H. P., Shim, J. H., Jeong, H. S., Lee, Y. H., Ham, Y. W., Han, S. B., & Hong, J. T. (2014). (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibits tumor growth via suppression of NF-jB and induction of death receptor 6. Apoptosis, 19(1), 165-178. https://doi.org/10.1007/s10495-013-0903-x