Differential effects of leptin on cancer in vitro.
BACKGROUND
Leptin, a protein produced by adipocytes, is an important signaling molecule in energy regulation and food intake. Many obese patients have leptin resistance associated with increased circulating leptin. Leptin receptor activation downregulates many regulatory genes, including STAT-3 and PAP 1. Certain cancers are associated with obesity, including breast, prostate, and colon. Recent studies have shown that leptin stimulates proliferation of human colon cancer in vitro. We hypothesized that leptin would have stimulatory effects on other human cancers.


METHODS
Human cancer cell lines from esophagus (KYSE410 and 150), breast (ZR75-1 and MCF-7), prostate (DU145 and PC-3), and pancreas (PANC-1, Mia-PaCa) were cultured using standard techniques. Leptin (0.4 ng/ml and 4.0 ng/ml) was added for 24 h and 48 h. Cell growth was determined by MTT assay. Statistical analysis was performed using analysis of variance.


RESULTS
Cancer cell lines demonstrated dose- and time-related responses to treatment. Leptin caused growth potentiation in breast, esophagus, and prostate cancer (P < 0.05). However, in both Mia-PaCa and PANC-1 pancreatic cancer cells, leptin inhibited growth (P < 0.05). This inhibitory effect peaked in PANC-1 at 48 h (78%).


CONCLUSIONS
We have shown for the first time that human cancer cells exhibit differential responses to treatment with leptin, depending upon organ of derivation. Both leptin and leptin antagonism have potential efficacy in cancer therapy, based on cellular origin. Further studies are warranted and ongoing.
Somasundar
Ponnandai
P
Louis A Johnson VA Medical Center 26506, Morgantown, West Virginia 26506, USA.
Yu
Alice K
AK
Vona-Davis
Linda
L
McFadden
David W
DW
D001943:Breast Neoplasms / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects*; D004938:Esophageal Neoplasms / Q000503:physiopathology; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009385:Neoplastic Processes; D010190:Pancreatic Neoplasms / Q000503:physiopathology; D000073718:Pancreatitis-Associated Proteins; D036361:Peptide Hormones / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000502:physiology
D020738:Leptin; D000073718:Pancreatitis-Associated Proteins; D036361:Peptide Hormones; C000612141:REG3A protein, human