Glutathione depletion or radiation treatment alters respiration and induces apoptosis in R3230Ac mammary carcinoma.
Glutathione depletion by L-buthionine sulfoximine inhibits the growth of Ehrlich mouse mammary carcinoma, R3230Ac rat mammary carcinoma and the PC3 human prostrate carcinoma cells, in vitro. Inhibition of growth occurs within the first 24 hours after exposure to the drug. The cell density does not increase over the initial cell density over 7 days. A549 human lung carcinoma and the DU145 human prostrate carcinoma cells show no inhibition of growth under the same treatment conditions. A comparative study of the R323OAc and A549 cells demonstrated a marked increase in apoptosis following L-BSO treatment in R3230Ac, which was dependent on L-BSO concentration and incubation time. L-BSO did not induce apoptosis in A549 cells at any of the concentrations tested. The incidence of apoptosis for R323OAc cells following exposure to 0.1 mM L-BSO was similar to the incidence of radiation-induced apoptosis observed after exposure to 10 Gy. Treatment with L-BSO or radiation alone inhibited O2 utilization in of R323Oac, while no effect on O2 utilization was observed in A549 cells. LBSO altered the bioreductive capacity of both the R323OAc and A549 cells. These results suggest that the ability of L-BSO to block mitochondrial O2 utilization may be involved in the apoptotic response in R3230Ac cells.
Biaglow
John E
JE
Departments of Biochemistry and Radiation Oncology, University of Pennsylvania Medical School, Philadelphia, Pa., USA.
Lee
Intae
I
Donahue
Jerry
J
Held
Kathy
K
Mieyal
John
J
Dewhirst
Mark
M
Tuttle
Steve
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014407:Tumor Cells, Cultured
D019328:Buthionine Sulfoximine; D005978:Glutathione