Programmed erythrocyte death following in vitro Treosulfan treatment.

Abstract

BACKGROUND/AIMS:

The cytotoxic drug Treosulfan is clinically used for the treatment of malignancy. A common side effect of Treosulfan treatment is anemia. Treosulfan is at least partially effective by triggering apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane. Triggers of eryptosis include oxidative stress, Ca(2+)-entry and increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The present study explored whether Treosulfan stimulates eryptosis, which may contribute to development of anemia.

METHODS:

Erythrocyte volume was estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from Fluorescein isothiocyanate (FITC)-annexin-V-binding, [Ca(2+)]i from Fluo3 fluorescence and reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA)-fluorescence.

RESULTS:

A 48 hours exposure of human erythrocytes to Treosulfan (800 µg/ml) significantly decreased erythrocyte forward scatter, increased the percentage of annexin-V-binding cells, increased [Ca(2+)]i, and increased ROS. The effect of Treosulfan on annexin-V-binding was virtually abrogated by removal of extracellular Ca(2+).

CONCLUSION:

Treosulfan stimulates suicidal erythrocyte death or eryptosis at least in part by inducing oxidative stress and stimulating Ca(2+) entry.

• Authors: Thomas Peter, Rosi Bissinger, Sigrid Enkel, Kousi Alzoubi, Gergely Oswald, Florian Lang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 35 Issue 4 Pg. 1372-80 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25720583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Aniline Compounds
• Antineoplastic Agents, Alkylating
• Phosphatidylserines
• Reactive Oxygen Species
• Xanthenes
• Fluo-3
• treosulfan
• Busulfan
• Fluorescein-5-isothiocyanate
• Calcium

Topics

• Aniline Compounds (chemistry)
• Antineoplastic Agents, Alkylating (pharmacology)
• Apoptosis (drug effects)
• Busulfan (analogs & derivatives, pharmacology)
• Calcium (metabolism)
• Erythrocytes (cytology, drug effects, metabolism)
• Flow Cytometry
• Fluorescein-5-isothiocyanate (chemistry)
• Humans
• Oxidative Stress (drug effects)
• Phosphatidylserines (metabolism)
• Reactive Oxygen Species (metabolism)
• Xanthenes (chemistry)