Article

Pharmacological enhancement of autophagy induced in a hepatocellular carcinoma cell line by high-LET radiation.

EA-3430, Université de Strasbourg, Centre Régional de Lutte contre le Cancer Paul Strauss, 3 rue de la porte de l'Hôpital, F-67065 Strasbourg, France.
Anticancer research (impact factor: 1.73). 02/2010; 30(2):303-10. pp.303-10
Source: PubMed

ABSTRACT The aim of the present study was to determine the cytotoxic consequences of high-linear energy transfer (LET) irradiation in the presence of oxaliplatin on hepatocellular carcinoma (HCC) cells in vitro. We attempted to correlate the induction of apoptosis and autophagy with the formation of DNA double-strand breaks (DSBs). SK-Hep1 cells were irradiated by 65 MeV neutrons in the presence of oxaliplatin and/or the poly(ADP-ribose) polymerase (PARP) inhibitor PJ34. DSBs were measured by the formation of gammaH2AX foci. Results show that in SK-Hep1 cells exposed to fast neutrons in the presence of oxaliplatin, DSBs occurred and persisted with time after irradiation. While apoptosis remained low in co-treated cells, autophagy was considerably increased after irradiation and augmented by the addition of oxaliplatin. Thus, autophagic cell death appears to play a prominent role in the cytotoxicity of the combined treatment and may be linked to the generation of heavy damage to DNA.

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Keywords

65 MeV neutrons
 
apoptosis
 
augmented
 
autophagic cell death
 
co-treated cells
 
correlate
 
cytotoxic consequences
 
cytotoxicity
 
DNA double-strand breaks
 
fast neutrons
 
gammaH2AX foci
 
hepatocellular carcinoma
 
high-linear energy transfer
 
irradiation
 
poly(ADP-ribose)
 
prominent role
 
SK-Hep1 cells
 
vitro