Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo

W. Scott Melvin, Laszlo G. Boros, Peter Muscarella, James L. Brandes, Jerome A. Johnson, William E. Fisher, William J. Schirmer, E. Christopher Ellison

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Abstract

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, CA V and Panc-1 were treated with concentrations of 1.9 μmol/L to 1000 μmol/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-1, 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 μmol/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 Pane-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.

Original languageEnglish (US)
Pages (from-to)392-397
Number of pages6
JournalSurgery
Volume121
Issue number4
DOIs
StatePublished - Apr 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery

Cite this

Melvin, W. S., Boros, L. G., Muscarella, P., Brandes, J. L., Johnson, J. A., Fisher, W. E., Schirmer, W. J., & Ellison, E. C. (1997). Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo. Surgery, 121(4), 392-397. https://doi.org/10.1016/S0039-6060(97)90308-1