Protolichesterinic acid, isolated from the lichen Cetraria islandica, reduces LRRC8A expression and volume-sensitive release of organic osmolytes in human lung epithelial cancer cells

Unnur Arna Thorsteinsdottir, Margret Thorsteinsdottir, Ian Henry Lambert*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalPhytotherapy Research
Volume30
Issue number1
Pages (from-to)97-104
Number of pages8
ISSN0951-418X
DOIs
Publication statusPublished - 2016

Keywords

  • arachidonic acid mobilization
  • Bax
  • C75
  • cisplatin
  • p21
  • taurine

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