The effect of AZT and chloroquine on the activities of ricin and a saporin-transferrin chimeric toxin.
This study deals with the combination of chloroquine (CQ, an anti-malaric drug) and 3'-azido-3'-deoxythymidine (AZT, anti-human immuno-deficiency virus (HIV) drug) with a chimeric toxin (TS) obtained by chemical linking of saporin (a ribosome inactivating protein from the plant Saponaria officinalis) and human transferrin, in the intoxication of the human chronic myeloid leukaemia cells (K562). Our data demonstrate that AZT, at concentrations comparable to those reached in the blood of HIV-infected patients under pharmacological treatment with this drug, can increase the toxicity of TS in cooperation with CQ inducing an increased effect on protein synthesis in K562 cells ( approximately 50% inhibition of protein synthesis for TS alone, and TS with AZT and approximately 70% with both AZT and CQ). Furthermore, pre-treatment of cells with AZT alone can induce an increase of apoptosis in K562 cells intoxicated with TS. By comparing data obtained with the model toxin ricin, we get indications that the two toxins partially differ in their intracellular routes, also suggesting that chimeric constructs containing ricin-like toxins (i.e. immunotoxins) could be coupled with the use of common and cheap drugs for the treatment of cancer in HIV-infected patients.
Department of Biomedical Sciences and Technologies, University of L'Aquila, Via Vetoio snc., loc. Coppito, 67010 L'Aquila, Italy.
A R
AR
Lizzi
A M
AM
D'Alessandro
N
N
Zeolla
F
F
Brisdelli
G
G
D'Andrea
G
G
Pitari
A
A
Oratore
A
A
Bozzi
R
R
Ippoliti
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002738:Chloroquine / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry*; D018613:Microscopy, Confocal; D009699:N-Glycosyl Hydrolases / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000633:toxicity*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014168:Transferrin / Q000737:chemistry*; D015215:Zidovudine / Q000494:pharmacology*
D000922:Immunotoxins; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D014168:Transferrin; D015215:Zidovudine; D002738:Chloroquine; D009699:N-Glycosyl Hydrolases; D000076985:Saporins