Drugs Exp Clin Res. 1992;18 Suppl:5-11.
Enhancement of macrophage tumouricidal activity by the alkaloid derivative
Ukrain. In vitro and in vivo studies.
Sotomayor EM, Rao K, Lopez DM, Liepins A.
Department of Microbiology and Immunology, University of Miami School of
Ukrain is a semisynthetic drug with immunomodulatory properties, derived from
Chelidonium majus L. alkaloids and thiophosphoric acid. The effect of this
compound on the growth of Balb/c syngenic mammary adenocarcinoma was assessed.
Intravenous, but not subcutaneous or intraperitoneal, administration of this drug
was found to be effective in delaying tumour growth in an actual therapeutic
protocol initiated five days after tumour implantation. No untoward side-effects
were observed using these in vivo treatment modalities. The role of macrophages
in the observed retardation of tumour development was investigated using
peritoneal exudate macrophages (PEM) in cytotoxicity assays. In previous studies,
the authors have found that PEM of mammary tumour bearing mice lose their
capacity to kill a variety of tumour target cells including the in vitro cultured
homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5
microM Ukrain for 24 h followed by stimulation with either IFN-gamma or with
LPS+IFN-gamma enhanced their cytotoxic activity. Treatment of PEM from tumour
bearing mice with 2.5 microM Ukrain and LPS results in a reversal of their
defective cytotoxic response against the DA-3 target cells. Furthermore, Ukrain
alone, in the absence of a secondary signal, induced the activation of
tumouricidal function of PEM from tumour bearing but not from normal mice. These
data indicate that Ukrain's in vivo effects against the development of mammary
tumours may be due, at least in part, to its ability to restore macrophage
Research Support, U.S. Gov't, P.H.S.