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

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BIOCHEMICAL PHARMACOLOGY
卷 196, 期 -, 页码 -

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114618

关键词

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

资金

  1. University of Turin, Italy [BIAF_RILO_18_01, BIA-F_RILO_19_01, GAMP_RILO_20_01]
  2. University of Milano Bicocca, Milan, Italy [2019-ATE-0481, 2020-ATE-0433]

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The role of 27-hydroxycholesterol (27OHC) in cancer development varies across different types of cancer, with potential harmful effects in breast cancer but anti-cancer effects in prostate cancer. Increased synthesis of 27OHC may promote the progression of late-stage cancers in colon, brain, and thyroid tissues.
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.

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