Oral dehydroepiandrosterone inhibits the growth of human pancreatic cancer in nude mice

Peter Muscarella, Laszlo G. Boros, William E. Fisher, Cameron Rink, W. Scott Melvin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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. Materials and 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 106 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 105-fold lower than previously reported. The mechanism of action may involve elevated concentrations of sex hormones.

Original languageEnglish (US)
Pages (from-to)154-157
Number of pages4
JournalJournal of Surgical Research
Volume79
Issue number2
DOIs
StatePublished - Oct 1998
Externally publishedYes

Fingerprint

Dehydroepiandrosterone
Pancreatic Neoplasms
Nude Mice
Growth
Gonadal Steroid Hormones
Diet
Tumor Burden
Progesterone
Testosterone
Poisons
Dietary Supplements
Intraperitoneal Injections
Heterografts
Androgens
Radioimmunoassay
Weight Loss
Rodentia
Animal Models
dehydroacetic acid

Keywords

  • Dehydroepiandrosterone
  • Pancreatic cancer

ASJC Scopus subject areas

  • Surgery

Cite this

Oral dehydroepiandrosterone inhibits the growth of human pancreatic cancer in nude mice. / Muscarella, Peter; Boros, Laszlo G.; Fisher, William E.; Rink, Cameron; Melvin, W. Scott.

In: Journal of Surgical Research, Vol. 79, No. 2, 10.1998, p. 154-157.

Research output: Contribution to journalArticle

Muscarella, Peter ; Boros, Laszlo G. ; Fisher, William E. ; Rink, Cameron ; Melvin, W. Scott. / Oral dehydroepiandrosterone inhibits the growth of human pancreatic cancer in nude mice. In: Journal of Surgical Research. 1998 ; Vol. 79, No. 2. pp. 154-157.
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abstract = "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. Materials and 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 106 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 105-fold lower than previously reported. The mechanism of action may involve elevated concentrations of sex hormones.",
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