Oral dehydroepiandrosterone inhibits the growth of human pancreatic cancer in nude mice.
BACKGROUND
Dehydroepiandrosterone (DHEA), an androgen precursor, inhibits the induction of pancreatic cancer in some animal models. Our laboratory has previously demonstrated that the sulfated form of DHEA (DHAS), when administered by intraperitoneal injection, inhibits the growth of pancreatic cancer xenografts in nude mice. In the present study, we hypothesize that DHEA-mediated pancreatic cancer growth inhibition is associated with alterations in plasma sex hormone concentrations.


METHODS
Forty male, nude, athymic mice were fed either Teklad 22/5 rodent diet or diet supplemented with 0.6% DHEA ad libitum. Four weeks following the institution of the experimental diets, 1 x 10(6) MiaPaCa-2 cells were injected into the right flank of each animal. Tumor area was recorded weekly and tumor weights were measured after 5 weeks. Plasma DHAS, testosterone, and progesterone concentrations were determined by radioimmunoassay.


RESULTS
Plasma DHAS, testosterone, and progesterone concentrations were all significantly elevated in the DHEA-treated group. DHEA-treated mouse plasma DHAS concentrations were approximately 50-fold higher than controls. Mean tumor weight was significantly reduced in the DHEA group (68.9 +/- 39.1 vs 121.0 +/- 64.3). DHEA treatment did not result in significant animal weight reductions and toxic side effects were not observed.


CONCLUSIONS
Dietary supplementation with 0.6% DHEA causes significant elevations in plasma DHAS concentration. DHEA administration significantly inhibits pancreatic cancer cell growth at plasma concentrations 1 x 10(5)-fold lower than previously reported. The mechanism of action may involve elevated concentrations of sex hormones.
Department of Surgery, The Ohio State University, Columbus, Ohio 43210, USA.
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Muscarella
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Boros
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Fisher
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Rink
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Melvin
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000473:pathology*; D011374:Progesterone / Q000097:blood; D012016:Reference Values; D013739:Testosterone / Q000097:blood
D000276:Adjuvants, Immunologic; D013739:Testosterone; D003687:Dehydroepiandrosterone; D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate