Τίτλος:
Saturated Hydroxy Fatty Acids Exhibit a Cell Growth Inhibitory Activity and Suppress the Cytokine-Induced β-Cell Apoptosis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The field of bioactive lipids is ever expanding with discoveries of novel lipid molecules that promote human health. Adopting a lipidomic-Assisted approach, two new families of previously unrecognized saturated hydroxy fatty acids (SHFAs), namely, hydroxystearic and hydroxypalmitic acids, consisting of isomers with the hydroxyl group at different positions, were identified in milk. Among the various regio-isomers synthesized, those carrying the hydroxyl at the 7-and 9-positions presented growth inhibitory activities against various human cancer cell lines, including A549, Caco-2, and SF268 cells. In addition, 7-and 9-hydroxystearic acids were able to suppress β-cell apoptosis induced by proinflammatory cytokines, increasing the possibility that they can be beneficial in countering autoimmune diseases, such as type 1 diabetes. 7-(R)-Hydroxystearic acid exhibited the highest potency both in cell growth inhibition and in suppressing β-cell death. We propose that such naturally occurring SHFAs may play a role in the promotion and protection of human health. © 2020 American Chemical Society. All rights reserved.
Συγγραφείς:
Kokotou, M.G.
Kokotos, A.C.
Gkikas, D.
Mountanea, O.G.
Mantzourani, C.
Almutairi, A.
Lei, X.
Ramanadham, S.
Politis, P.K.
Kokotos, G.
Περιοδικό:
Journal of Medicinal Chemistry
Εκδότης:
American Chemical Society
Λέξεις-κλειδιά:
1 (benzyloxy)hexadecan 10 ol; 1 (benzyloxy)hexadecan 7 ol; 1 (benzyloxy)hexadecan 7 yl acetate; 1 (benzyloxy)octadecan 10 ol; 1 (benzyloxy)octadecan 7 ol; 1 hydroxyhexadecan 7 yl acetate; 1 hydroxyoctadecan 7 yl acetate; 10 acetoxyhexadecanoic acid; 10 acetoxyoctadecanoic acid; 10 hydroxyoctadecanoic acid; 16 (benzyloxy)hexadecan 7 yl acetate; 16 hydroxyhexadecan 7 yl acetate; 18 (benzyloxy)octadecan 9 yl acetate; 18 hydroxyoctadecan 9 yl acetate; 2 [6 (benzyloxy)hexyl]oxirane; 2 [9 (benzyloxy)nonyl]oxirane; 7 acetoxyhexadecanoic acid; 7 acetoxyoctadecanoic acid; 7 hydroxyhexadecanoic acid; 7 hydroxyoctadecanoic acid; antidiabetic agent; antineoplastic agent; cytokine; hydroxy fatty acid; saturated fatty acid; unclassified drug; cytokine; fatty acid; STAT3 protein; stearic acid; stearic acid derivative, A-549 cell line; antidiabetic activity; antineoplastic activity; apoptosis; Article; autoimmune disease; blood sampling; Caco-2 cell line; cancer inhibition; colon adenocarcinoma; comparative study; controlled study; drug potency; drug screening; drug synthesis; enantioselectivity; HT-29 cell line; human; human cell; inflammation; insulin dependent diabetes mellitus; isomer; lipidomics; mass spectrometry; MTT assay; pancreas islet beta cell; retention time; SF268 cell line; signal transduction; animal; apoptosis; cell line; cell proliferation; chemistry; cytology; drug effect; gene expression; genetics; high performance liquid chromatography; metabolism; milk; pancreas islet beta cell; stereoisomerism; synthesis; tandem mass spectrometry, Animals; Apoptosis; Cell Line; Cell Proliferation; Chromatography, High Pressure Liquid; Cytokines; Fatty Acids; Gene Expression; Humans; Insulin-Secreting Cells; Milk; STAT3 Transcription Factor; Stearic Acids; Stereoisomerism; Tandem Mass Spectrometry
DOI:
10.1021/acs.jmedchem.0c00844
