Simulated microgravity induces programmed cell death in human thyroid carcinoma cells.
The present study focused on the effects of simulated microgravity on the human follicular thyroid carcinoma cell line ML-1. Cultured on a three-dimensional clinostat ML- 1 cells formed three-dimensional multicellular tumor spheroids (MCTS: 0.3 +/= 0.01mm in diameter). Furthermore, ML-1 cells grown on the clinostat showed elevated amounts of the apoptosis-associated Fas protein, of p53 and of bax, but reduced quantities of bcl-2. In addition, signs of apoptosis as assessed by TdT-mediated DUTP digoxigenin nick end labeling, DAPI staining, DNA laddering and 85-kDa apoptosis-related DNA fragments became detectable. The latter ones resulted from enhanced 116-kDa poly(ADP-ribose)polymerase activity. Electron microscopy revealed all morphological signs of apoptosis. Caspase 3 was clearly upregulated. In conclusion, our experiments show that conditions of simulated microgravity induce early programmed cell death and use different pathways of apoptosis.
Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universitat Berlin, Germany. pkossmeh@zedat.fu-berlin.de
Peter
P
Kossmehl
Mehdi
M
Shakibaei
Augusto
A
Cogoli
Holger
H
Pickenhahn
Martin
M
Paul
Daniela
D
Grimm