TY - JOUR
T1 - Oral dehydroepiandrosterone inhibits the growth of human pancreatic cancer in nude mice
AU - Muscarella, Peter
AU - Boros, Laszlo G.
AU - Fisher, William E.
AU - Rink, Cameron
AU - Melvin, W. Scott
N1 - Funding Information:
This investigation was supported by the National Cancer Institute, National Research Service Award CA-09338, Division of Cancer Prevention and Control. Other funding was supplied by grants from the Ohio Division of the American Cancer Society, the Bremer Foundation at the Ohio State University, and Surgical Research Incorporated, Columbus, OH.
PY - 1998/10
Y1 - 1998/10
N2 - 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.
AB - 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.
KW - Dehydroepiandrosterone
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=0032190016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032190016&partnerID=8YFLogxK
U2 - 10.1006/jsre.1998.5417
DO - 10.1006/jsre.1998.5417
M3 - Article
C2 - 9758731
AN - SCOPUS:0032190016
SN - 0022-4804
VL - 79
SP - 154
EP - 157
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -