Protolichesterinic Acid, Isolated from the Lichen Cetraria islandica, Reduces LRRC8A Expression and Volume-Sensitive Release of Organic Osmolytes in Human Lung Epithelial Cancer Cells.

Autor: Thorsteinsdottir UA; Department of Biology, Section of Cell biology and Physiology, University of Copenhagen, 13 Universitetsparken, Copenhagen, DK-2100, Denmark.; School of Health Sciences, Faculty of Pharmaceutical Sciences, University of Iceland, 101, Reykjavik, Iceland., Thorsteinsdottir M; School of Health Sciences, Faculty of Pharmaceutical Sciences, University of Iceland, 101, Reykjavik, Iceland., Lambert IH; Department of Biology, Section of Cell biology and Physiology, University of Copenhagen, 13 Universitetsparken, Copenhagen, DK-2100, Denmark.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2016 Jan; Vol. 30 (1), pp. 97-104. Date of Electronic Publication: 2015 Nov 09.
DOI: 10.1002/ptr.5507
Abstrakt: We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 µg/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 → 200 mOsm) by 60%. C75 (20 µg/mL, 24 h), a γ-lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 µg/mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to γ-lactone's inhibitory action. 5-Lipoxygenase (5-LO) activity is essential for swelling-induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5-HETE/LTB4 ) under hypotonic conditions, excluding that PA mediated inhibition of VSOAC involves 5-LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 μM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3-, 1.5- and 3.3-fold increase in the expression of LRRC8A, Bax (regulator of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro-apoptotic drug in A549 cells.
(Copyright © 2015 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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