Role of 27-hydroxycholesterol and its metabolism in cancer progression: Human studies

Biochem Pharmacol. 2022 Feb:196:114618. doi: 10.1016/j.bcp.2021.114618. Epub 2021 May 21.

Abstract

Direct translation of findings achieved in experimental cell or animal models to humans is quite a difficult task. We focused here only on the epidemiological and ex vivo human studies so far available about the role of 27-hydroxycholesterol (27OHC) and related metabolism in cancer development. Some studies point to an adverse effect of 27OHC in breast cancer, based on the oxysterol's recognized ability to bind to and modulate estrogen receptors. The detrimental role of this side chain oxysterol would be evident in cancer progression, mainly in post-menopausal women and in an advanced stage of the disease. Other human researches, however, would rather correlate 27OHC intra-tumoral levels to a better prognosis. The analyses on human prostate cancer specimens performed to date are all against a detrimental contribution of 27OHC, rather suggesting interesting anti-prostate cancer effects exerted by this oxysterol. Finally, an increased 27OHC synthesis on the contrary seems to favour progression of late stage cancers in colon, brain and thyroid tissues, as found for breast cancer, possibly due to pro-inflammatory and pro-survival signalling triggered by disproportionate amounts of this oxysterol.

Keywords: 27-Hydroxycholesterol; Cancer progression; Cytochrome P450 27A1 (CYP27A1); Cytochrome P450 7B1 (CYP7B1); Human studies; Oxysterol metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Cholestanetriol 26-Monooxygenase / metabolism
  • Cytochrome P450 Family 7 / metabolism
  • Disease Progression*
  • Humans
  • Hydroxycholesterols / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Steroid Hydroxylases / metabolism

Substances

  • Biomarkers, Tumor
  • Hydroxycholesterols
  • 27-hydroxycholesterol
  • Steroid Hydroxylases
  • Cytochrome P450 Family 7
  • CYP7B1 protein, human
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase