Triggering of Suicidal Erythrocyte Death by Regorafenib

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Jens ZierleFlorian Lang

Abstract

The multikinase inhibitor regorafenib is utilized for the treatment of malignancy. The substance is effective in part by triggering suicidal death or apoptosis of tumor cells. Side effects of regorafenib include anemia. At least in theory, regorafenib induced anemia could result from stimulated suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and ceramide. The present study explored, whether regorafenib induces eryptosis and, if so, whether it is effective up- and/or downstream of Ca2+. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. A 48 hours exposure of human erythrocytes to regorafenib (≥ 0.5 µg/ml) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter (≥ 1.25 µg/ml), but did not significantly increase Fluo3-fluorescence, DCFDA fluorescence or ce...Continue Reading

Citations

Jun 14, 2016·Cell Biochemistry and Function·Elena SignorettoFlorian Lang
Feb 20, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Majed AbedAlfred Königsrainer
Feb 22, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Mustafa AlmasryCaterina Faggio
May 26, 2017·International Journal of Cancer. Journal International Du Cancer·Elisabeth LangFlorian Lang

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