Lovastatin effects on human breast carcinoma cells. Differential toxicity of an adriamycin-resistant derivative and influence on selenocysteine tRNAS.
Selenocysteine tRNA[Ser]Sec isoacceptors contain the modified nucleotide i6A immediately 3' to the anticodon. Because synthesis of i6A is expected to be inhibited by lovastatin, the status of tRNA[Ser]Sec isoacceptors was examined in human breast carcinoma cells. As part of the initial characterization of these cells, it was determined that an adriamycin resistant derivative of the MCF-7 cell line exhibited a dramatic increase in the sensitivity to the killing effects of lovastatin relative to the parental MCF-7 cells. When MCF-7Adr cells were incubated with high levels of lovastatin, there was a dramatic perturbation in the distribution of isoacceptors within the selenocysteine tRNA population. Lovastatin may therefore be a useful reagent for both the study of differential killing of drug-resistant tumor cells and selenoprotein biosynthesis.
Diamond
A M
AM
Department of Radiation and Cellular Oncology, University of Chicago, IL 60637, USA.
Jaffe
D
D
Murray
J L
JL
Safa
A R
AR
Samuels
B L
BL
Hatfield
D L
DL
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000737:chemistry*; D002277:Carcinoma / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008148:Lovastatin / Q000633:toxicity*; D012345:RNA, Transfer, Amino Acid-Specific / Q000032:analysis*; D012643:Selenium / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D012345:RNA, Transfer, Amino Acid-Specific; C036928:tRNA, selenocysteine-; D004317:Doxorubicin; D008148:Lovastatin; D005979:Glutathione Peroxidase; D012643:Selenium