Peptide YY inhibits growth of human breast cancer in vitro and in vivo.
BACKGROUND
Hormonal manipulation is important in the treatment of breast cancer. Gastrointestinal hormones may have antiproliferative effects on malignancies arising outside the gastrointestinal tract. Peptide YY (PYY) suppresses growth of, and levels of, intracellular cyclic adenosine monophosphate (cAMP) in pancreatic adenocarcinoma. We hypothesized that PYY would inhibit growth of breast cancer.


METHODS
MCF-7 human breast infiltrative ductal carcinoma cells in 96-well plates were treated with PYY at 1.25 pmol/mcl. Control wells received an equal volume of bovine serum albumin to mimic experimental conditions. 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 described above. Intracellular cAMP levels in cell lysates were determined with a tritiated cAMP assay. One million MCF-7 cells were injected into mammary fat pads of 20 female athymic nude mice. Pellets releasing PYY at 400 pmol/kg/h were placed subcutaneously in 10 mice 24 h prior to cell inoculation. Tumors were harvested after 21 days, weighed, and measured with vernier calipers.


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 PYY-treated mice (P < 0.006); volume of PYY-exposed tumors was one-third that of controls (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 intracellular cAMP levels may contribute to the observed suppression of cell proliferation.
Grisé
K R
KR
University of California at Los Angeles Medical Center, Los Angeles, California, 90095, USA.
Rongione
A J
AJ
Laird
E C
EC
McFadden
D W
DW
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D004396:Coloring Agents; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D019894:Peptide YY / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D019894:Peptide YY; D000242:Cyclic AMP; C022616:thiazolyl blue