Elimination of Ehrlich tumours by ATP-induced growth inhibition, glutathione depletion and X-rays.
ATP-induced tumour growth inhibition is accompanied by a selective decrease in the content of the tripeptide glutathione (GSH) within the cancer cells in vivo. Depletion of cellular GSH sensitizes tumours to chemotherapy and radiation, but the usefulness of this depletion depends on whether the levels of GSH can be reduced in the tumour relative to normal tissues. We report here that administration of ATP in combination with diethylmaleate and X-rays leads to complete regression of 95% of Ehrlich ascites tumours in mice. This shows that an aggressive tumour can be eliminated by using a therapy based on modulation of GSH levels in cancer cells.
Estrela
J M
JM
Departamento de Fisiología, Universidad de Valencia, Facultad de Medicina, Spain.
Obrador
E
E
Navarro
J
J
Lasso De la Vega
M C
MC
Pellicer
J A
JA
D000255:Adenosine Triphosphate / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019328:Buthionine Sulfoximine; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000037:antagonists & inhibitors*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008298:Maleates / Q000627:therapeutic use; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000627:therapeutic use; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D014965:X-Rays
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008298:Maleates; D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D000255:Adenosine Triphosphate; D005721:Glutamate-Cysteine Ligase; C014476:diethyl maleate; D005978:Glutathione