Tripeptide tyroserleutide enhances the antitumor effects of macrophages and stimulates macrophage secretion of IL-1β, TNF-α, and NO in vitro

Tyroserleutide (YSL) is a type of active, low molecular weight polypeptide, comprised of three amino acids, which has antitumor effects. YSL has various advantages over the other bioactive peptides such as its low molecular weight, simple construction, nonimmunogenicity, specificity, few side effects, and ease of synthesis. However, the biological activities contributing to it’s antitumor effects are not yet known. We studied the effects of YSL on the in vitro cytotoxic activity of BALB/c mice peritoneal macrophages (PEMφ) against the target tumor cell lines BEL-7402 and B16-F10. We also measured the concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nitric oxide (NO) produced by YSL-activated Mφ, and we determined the concentrations of IL-1β and NO secreted by YSL-activated murine macrophage RAW264.7 cells. YSL activated Mφ in vitro, inhibited BEL-7402 proliferation, enhanced PEMφ antitumor effects, and stimulated IL-1β, TNF-α, and NO production by RAW264.7 cells. These data suggest that YSL activates the monocyte–macrophage system, which enhances Mφ antitumor effects against BEL-7402 and B16-F10 cells and stimulates the secretion by Mφ of cytotoxic effectors such as IL-1β, TNF-α, and NO.