Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Sep 3;10(9):2301.
doi: 10.3390/cells10092301.

Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status

Fábio Alessandro de Freitas  1 , Débora Levy  1 , Amira Zarrouk  2 , Gérard Lizard  3 , Sérgio Paulo Bydlowski  1   4
Affiliations
Review

Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status

Fábio Alessandro de Freitas et al. Cells. .

Abstract

Oxysterols are oxidized derivatives of cholesterol produced by enzymatic activity or non-enzymatic pathways (auto-oxidation). The oxidation processes lead to the synthesis of about 60 different oxysterols. Several oxysterols have physiological, pathophysiological, and pharmacological activities. The effects of oxysterols on cell death processes, especially apoptosis, autophagy, necrosis, and oxiapoptophagy, as well as their action on cell proliferation, are reviewed here. These effects, also observed in several cancer cell lines, could potentially be useful in cancer treatment. The effects of oxysterols on cell differentiation are also described. Among them, the properties of stimulating the osteogenic differentiation of mesenchymal stem cells while inhibiting adipogenic differentiation may be useful in regenerative medicine.

Keywords: apoptosis; autophagy; cell death; differentiation; mesenchymal stem cells; oxiapoptophagy; oxysterols.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Oxysterol 2D molecules representations. (A) 24(S),25-epoxycholesterol; (B) 24(S)-hydroxycholesterol; (C) 25-hydroxycholesterol; (D) 27-hydroxycholesterol; (E) 7-hydroperoxycholesterol; (F) 7-ketocholesterol; (G) 7β-hydroxycholesterol; (H) 7α-hydroxycholesterol; (I) 7α,25-dihydroxycholesterol; (J) 22(S)-hydroxycholesterol; (K) 24-oxocholesterol; (L) 20(S)-hydroxycholesterol; (M) 4β-hydroxycholesterol; and (N) 5,6-epoxycholesterol; (O) 24-oxocholesterol. Source: PubChem; URL: https://pubchem.ncbi.nlm.nih.gov; last accessed, 5 August 2021.
Figure 2
Figure 2
Schematic representation of synthesis of some oxysterols via enzymatic and non-enzymatic pathways.
Figure 3
Figure 3
Schematic representation of the three main types of cell death: autophagy, apoptosis, and necrosis. TNF (tumor necrosis factor); FAS (CD95); FAS-L (CD95-ligand); TRAIL (TNF-related apoptosis-inducing ligand); TNFR (TNF receptor); ROS (reactive oxygen species); FADD (Fas-associated death domain); TRADD (TNFR-associated death domain); RIPK (receptor-interacting protein kinase); MLKL (mixed lineage kinase domain-like protein); DISC (death-inducing signaling complex).
See this image and copyright information in PMC

References

    1. Faletrov Y.V., Efimova V.S., Horetski M., Tugaeva K.V., Frolova N.S., Lin Q., Isaeva L.V., Rubtsov M.A., Sluchanko N.N., Novikova L.A., et al. New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells. Chem. Phys. Lipids. 2019;227:104850. doi: 10.1016/j.chemphyslip.2019.104850. - DOI - PubMed
    1. Levy D., Melo T., Ohira B.Y., Fidelis M.L., Ruiz J., Rodrigues A., Bydlowski S.P. Oxysterols selectively promote short-term apoptosis in tumor cell lines. Biochem. Biophys. Res. Commun. 2018;505:1043–1049. doi: 10.1016/j.bbrc.2018.10.008. - DOI - PubMed
    1. Perego C., Da Dalt L., Pirillo A., Galli A., Catapano A.L., Norata G.D. Cholesterol metabolism, pancreatic β-cell function and diabetes. Biochimica Biophysica Acta (BBA)-Mol. Basis Dis. 2019;1865:2149–2156. doi: 10.1016/j.bbadis.2019.04.012. - DOI - PubMed
    1. Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat. Rev. Mol. Cell Biol. 2008;9:125–138. doi: 10.1038/nrm2336. - DOI - PubMed
    1. Lyu J., Yang E.J., Shim J.S. Cholesterol Trafficking: An Emerging Therapeutic Target for Angiogenesis and Cancer. Cells. 2019;8:389. doi: 10.3390/cells8050389. - DOI - PMC - PubMed

Publication types

LinkOut - more resources