Your browser doesn't support javascript.
loading
Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo.
Melvin, W S; Boros, L G; Muscarella, P; Brandes, J L; Johnson, J A; Fisher, W E; Schirmer, W J; Ellison, E C.
Afiliación
  • Melvin WS; Division of General Surgery, Ohio State University, Columbus, USA.
Surgery ; 121(4): 392-7, 1997 Apr.
Article en En | MEDLINE | ID: mdl-9122868
ABSTRACT

BACKGROUND:

Dehydroepiandrosterone-sulfate (DHEA-S) is a potent inhibitor of glucose-6 phosphate dehydrogenase, the rate limiting enzyme of the hexose monophosphate shunt, a biochemical pathway that provides substrate for DNA synthesis in neoplastic tissue. DHEA-S has been shown to inhibit the growth of neoplasms arriving from human skin, lung, colon, and mammary tissue. This study evaluates the effect of DHEA-S on human pancreatic cancer cell lines in vitro and in vivo.

METHODS:

In vitro, the human pancreatic adenocarcinoma cell lines MiaPaCa-2, Capan-1, Capan-2, CAV and Panc-1 were treated with concentrations of 1.9 mumol/L to 1000 mumol/L DHEA-S in 1% dimethylsulfoxide (DMSO) for 5 consecutive days. Cell proliferation was determined by a nonradioactive cell proliferation assay and compared with DMSO treated controls. In vivo testing was performed by inoculating two cell lines, MiaPaCa-2 and Panc-I, into the flank of 40 male nude athymic mice in four study groups. After 1 week of growth, 667 mg/kg DHEA-S in 1% DMSO or 0.2 ml 1% DMSO alone in the control group was administered by daily intraperitoneal injection. Body weight and tumor size was recorded weekly, and tumor weight was measured after 3 weeks of treatment.

RESULTS:

In vitro cell proliferation was decreased in the five cell lines by 36% to 62% of controls (p < 0.001) at 500 mumol/L DHEA-S. In vivo, after 2 weeks, tumor size was only 76% (p < 0.008) and 67% (p < 0.005) of the controls. After 3 weeks of treatment, tumor size was 73% (p < 0.001) and 53% (p < 0.001) of controls, and tumor weight was decreased by 73% in MiaPaCa-2 (p < 0.001) and 66% in Panc-1 (p < 0.001). Radioimmunoassay measurements of DHEA-S and testosterone from DHEA-S treated mouse plasma showed a significant increase in circulating levels of these hormones.

CONCLUSIONS:

DHEA-S achieves high serum levels after intraperitoneal injection without elevation of serum testosterone levels and produces no significant toxicity. Treatment with DHEA-S results in a significant reduction of proliferation of human pancreatic cancer cells in culture and when grown as subcutaneous tumors in athymic nude mice.
Asunto(s)
Buscar en Google
Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Adenocarcinoma / Sulfato de Deshidroepiandrosterona / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Surgery Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos
Buscar en Google
Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Adenocarcinoma / Sulfato de Deshidroepiandrosterona / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Surgery Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos