Recent evidence has implicated
enkephalins as
immunomodulators. Several studies have reported the regulation of
tumor growth by
methionine enkephalin (ME). However, there has been little effort to relate the immunological significance of
enkephalins to the development of anticancer drugs. The present study had three aims: first, to compare the antitumor activity of the synthetic
peptide, D-[Ala2]
methionine enkephalinamide (MEA), with endogenous
enkephalins on PYB6
fibrosarcoma tumor growth; second, to determine whether
tumor growth inhibition was mediated by an
opiate receptor; and third, to investigate the effects of MEA on selected immune responses. Female B6C3F1 mice were injected i.p. daily for 7 days with 50-4000 micrograms/kg of ME, MEA,
leucine enkephalin (LE) or D-[Ala2]
leucine enkephalinamide (LEA), beginning 1 day after PYB6 inoculation. ME and MEA, but not LE or LEA, decreased the PYB6 growth rate. The dose of 50 micrograms/kg MEA exerted the maximum inhibition of
tumor growth (nearly 72% on day 15 post
tumor transplantation). MEA was not directly toxic to PYB6
tumor cells, as evaluated by the measurement of
DNA synthesis and cellular
ATP levels of PYB6 cells exposed to MEA in vitro. No [3H]-
etorphine specific bindings were detected on the cell membrane or sonicates of splenic lymphocytes or PYB6 cells. Therefore, the antitumor activity by MEA is likely mediated by an indirect mechanism. Immunological studies indicated that MEA selectively enhanced the lymphoproliferative response to the T-cell
mitogen,
concanavalin A, but not to the B-cell
mitogen,
lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)