Actinonin induces apoptosis in U937 leukemia cells

Grujic, Mirjana; Zavasnik-Bergant, Tina; Pejler, Gunnar; Renko, Metka

doi:10.1016/j.canlet.2004.10.048

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Volume 223, Issue 2 , Pages 211-218, 8 June 2005

Actinonin induces apoptosis in U937 leukemia cells

Mirjana Grujic
- Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences, BMC, Box 575, 75123 Uppsala, Sweden
- Corresponding author. Present address: Department of Molecular Biosciences, Swedish University of Agricultural Sciences, BMC, Box 575, 75123 Uppsala, Sweden. Tel.: +46 18 471 4192; fax: +46 18 55 0762.
Tina Zavasnik-Bergant
- Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia
Gunnar Pejler
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences, BMC, Box 575, 75123 Uppsala, Sweden
Metka Renko
- Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

Received 30 September 2004; received in revised form 22 October 2004; accepted 24 October 2004.

Abstract

We have previously shown that actinonin causes inhibition of cellular proliferation in U937 leukemia cells. In this report we demonstrate that the inhibition of cell growth by actinonin occurs through the induction of apoptosis. Signs of apoptosis at high actinonin concentration included DNA fragmentation, exposure of phosphatidylserine and condensation of cell nuclei. Apoptosis caused by actinonin was inhibited by Z-VAD-FMK, a broad specificity inhibitor of caspases, implicating the caspase pathway of apoptosis. Further, apoptosis was associated with a large increase in intracellular caspase-3 and -7 activities.

Keywords: Actinonin, Apoptosis, Leukemia