Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure.

Abstract

BACKGROUND/AIMS:

The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis.

METHODS:

Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofuorescein diacetate (DCFDA) fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit.

RESULTS:

A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml) significantly increased the percentage of annexin-V-binding cells (to 9.3 ± 0.9 %) and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca(2+)]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM) and SB203580 (2 µM).

CONCLUSIONS:

Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.

• Authors: Salvatrice Calabrò, Kousi Alzoubi, Caterina Faggio, Stefan Laufer, Florian Lang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 37 Issue 1 Pg. 131-42 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26303375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Annexin A5
• Ceramides
• Hemoglobins
• Imidazoles
• Pyridines
• Reactive Oxygen Species
• Triterpenes
• boswellic acid
• Adenosine Triphosphate
• p38 Mitogen-Activated Protein Kinases
• SB 203580
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Annexin A5 (metabolism)
• Calcium (metabolism)
• Cell Death (drug effects)
• Cell Size (drug effects)
• Ceramides (metabolism)
• Cytosol (drug effects, metabolism)
• Erythrocyte Membrane (drug effects, metabolism)
• Erythrocytes (drug effects, metabolism)
• Hemoglobins (metabolism)
• Hemolysis (drug effects)
• Humans
• Imidazoles (pharmacology)
• Pyridines (pharmacology)
• Reactive Oxygen Species (metabolism)
• Triterpenes (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)