Peptide YY inhibits growth of human breast cancer in vitro and in vivo

Background. Hormonal manipulation is important in the treatment of breast c ancer. Gastrointestinal hormones may have antiproliferative effects on mali gnancies arising outside the gastrointestinal tract. Peptide YY (PYY) suppr esses growth of, and levels of, intracellular cyclic adenosine monophosphat e (cAMP) in pancreatic adenocarcinoma. We hypothesized that PYY would inhib it growth of breast cancer. Materials and methods. MCF-7 human breast infiltrative ductal carcinoma cel ls in 96-well plates were treated with PYY at 1.25 pmol/mu l. Control wells received an equal volume of bovine serum albumin to mimic experimental con ditions. In vitro survival was determined by MTT assays, which reflect cell viability by measuring mitochondrial NADH-dependent dehydrogenase activity . MCF-7 cells in six-well plates were treated with PYY or albumin as descri bed above. Intracellular cAMP levels in cell lysates were determined with a tritiated cAMP assay. One million MCF-7 cells were injected into mammary f at pads of 20 female athymic nude mice. Pellets releasing PYY at 400 pmol/k g/h were placed subcutaneously in 10 mice 24 h prior to cell inoculation. T umors were harvested after 21 days, weighed, and measured with vernier cali pers. Results. PYY reduced in vitro growth by 40% (P < 0.001). Intracellular cAMP levels in PYY-treated cells were 62.4% less than those of controls (P < 0. 001). Tumors from control mice weighed twice as much as those from PW-treat ed mice (P < 0.006); volume of PW-exposed tumors was one-third that of cont rols (P < 0.005). Conclusions. PYY inhibits growth of breast cancer in vitro and in vivo and may be of benefit in the treatment of this malignancy. The reduction in int racellular cAMP levels may contribute to the observed suppression of cell p roliferation, (C) 1999 Academic Press.