Enhancement of macrophage tumouricidal activity by the alkaloid derivative Ukrain. In vitro and in vivo studies

M. E. Sotomayor, K. Rao, D. M. Lopez, A. Liepins

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22 Scopus citations

Abstract

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 2.5μM Ukrain for 2.5h followed by stimulation with either IFN-γ or with LPS+IFN-γ enhanced their cytotoxic activity. Treatment of PEM from tumour bearing mice with 2.5μM 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 cytolytic function.

Original languageEnglish (US)
Pages (from-to)5-11
Number of pages7
JournalDrugs under Experimental and Clinical Research
Volume18
Issue numberSUPPL.
StatePublished - 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)

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