Cr. Wagner et al., POTENT GROWTH-INHIBITORY ACTIVITY OF ZIDOVUDINE ON CULTURED HUMAN BREAST-CANCER CELLS AND RAT MAMMARY-TUMORS, Cancer research, 57(12), 1997, pp. 2341-2345
Originally designed as an antitumor agent, zidovudine (AZT) has exhibi
ted only marginal tumor growth inhibitory activity. Recently, three ab
stracts have described positive clinical outcomes for a small number o
f patients with advanced breast cancer treated with weekly infusions o
f either methotrexate or cisplatin and AZT. Consequently, we conducted
a preclinical study of the anti-breast cancer and anti-mammary tumor
activity of AZT. Here we have demonstrated that AZT, alone, has a pref
erential in vitro and in vivo effect on breast and mammary cancer cell
s. It is 1000 times as potent as an inhibitor of the in vitro growth o
f the human breast cancer cell line MCF-7 (IC50 = 10 +/- 5 nM) than of
the growth of the T-cell leukemia cell line CEM (IC50 = 14 +/- 2 mu M
). A novel mechanism for this preferential effect on growth is indicat
ed by the 3-4-fold increase in production of phosphorylated AZT (mono-
, di-, and triphosphate) in MCF-7 relative to CEM. We extended these i
n vitro observations to iii vivo studies in rats and found that AZT is
a potent ill vivo inhibitor of the growth of methylnitrosourea-induce
d rat mammary tumors without any apparent toxic effects on internal or
gans. These preclinical results demonstrate, for the first time, that
AZT has significant anti-breast cancer activity and strongly suggest t
hat the clinical usefulness of this drug is worthy of investigation.