ΔNp63α mediates sulforaphane suppressed colorectal cancer stem cell properties through transcriptional regulation of Nanog/Oct4/Sox2

J Nutr Biochem. 2022 Sep:107:109067. doi: 10.1016/j.jnutbio.2022.109067. Epub 2022 May 21.

Abstract

Cancer stem cells (CSCs) play a key role in cancer initiation, development, metastasis, and recurrence. Previously, we found that sulforaphane (SFN), a natural compound obtained from cruciferous vegetables, inhibited colorectal CSCs via the downregulation of TAp63α. However, the role of ΔNp63α, another critical isoform of p63 which has been considered to contribute to cancer progression, in SFN-mediated colorectal CSCs inhibition remains unclear. Here, we showed that ΔNp63α expression was enhanced in sphere-forming colorectal cancer cells. Overexpression of ΔNp63α promoted the properties of CSCs, while downregulation of ΔNp63α suppressed those properties. Besides, ΔNp63α was found to activate the transcription of core CSCs genes including Nanog, Oct4, and Sox2. Furthermore, in vitro and in vivo experiments illustrated the regulatory effects of SFN on ΔNp63α and colorectal CSCs. These findings suggested for the first time that ΔNp63α activated the transcription of Nanog, Oct4, Sox2 and mediated the interventional effects of SFN on colorectal CSCs, thus providing a novel mechanism by which SFN inhibits colorectal CSCs.

Keywords: colorectal cancer stem cells; sulforaphane; ΔNp63α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Humans
  • Isothiocyanates / pharmacology
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Neoplastic Stem Cells* / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • SOXB1 Transcription Factors / pharmacology
  • Sulfoxides / pharmacology

Substances

  • Isothiocyanates
  • NANOG protein, human
  • Nanog Homeobox Protein
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Sulfoxides
  • sulforaphane