Effects of cyclosporine and α-difluoromethylornithine on the growth of mouse colon cancer in vitro

Rami Saydjari; Courtney M. Townsend; Sam C. Barranco

doi:10.1016/0024-3205(87)90137-8

Effects of cyclosporine and α-difluoromethylornithine on the growth of mouse colon cancer in vitro

Rami Saydjari
, Courtney M. Townsend
, Sam C. Barranco

Surgery

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. α-Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3×10^-4 mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer.

Original language	English (US)
Pages (from-to)	359-366
Number of pages	8
Journal	Life Sciences
Volume	40
Issue number	4
DOIs	https://doi.org/10.1016/0024-3205(87)90137-8
State	Published - Jan 26 1987

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics
General Biochemistry, Genetics and Molecular Biology

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10.1016/0024-3205(87)90137-8

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@article{26b53b4eaa58449a987326f309339a8e,

title = "Effects of cyclosporine and α-difluoromethylornithine on the growth of mouse colon cancer in vitro",

abstract = "The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. α-Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3×10-4 mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer.",

author = "Rami Saydjari and Townsend, \{Courtney M.\} and Barranco, \{Sam C.\}",

note = "Funding Information: The DFMO was the generous gift of W.J. Nudak, Ph.D., Manager of Research Information, Merrell Research Center, Cincinnati, OH. Cyclosporine was provided by David L. Winter, M.D., Director of Medical Research Information at the Sandoz Research Institute, East Hanover, NJ. We would also like to thank Elena J. Glass and Pamella J. Ford for their technical assistance, and Mary Lou Mraz for her assistance in the preparation of this manuscript. Supported by grants from the National Institutes of Health (R01DK 15241, POI DK5608, and RCDA CA 00854), the American Cancer Society (PDT-220), and from the National Cancer Institute (ROI CA 15397), and in conjunction with the Walls Medical Research Foundation, Houston, Texas.",

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doi = "10.1016/0024-3205(87)90137-8",

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T1 - Effects of cyclosporine and α-difluoromethylornithine on the growth of mouse colon cancer in vitro

AU - Saydjari, Rami

AU - Townsend, Courtney M.

AU - Barranco, Sam C.

N1 - Funding Information: The DFMO was the generous gift of W.J. Nudak, Ph.D., Manager of Research Information, Merrell Research Center, Cincinnati, OH. Cyclosporine was provided by David L. Winter, M.D., Director of Medical Research Information at the Sandoz Research Institute, East Hanover, NJ. We would also like to thank Elena J. Glass and Pamella J. Ford for their technical assistance, and Mary Lou Mraz for her assistance in the preparation of this manuscript. Supported by grants from the National Institutes of Health (R01DK 15241, POI DK5608, and RCDA CA 00854), the American Cancer Society (PDT-220), and from the National Cancer Institute (ROI CA 15397), and in conjunction with the Walls Medical Research Foundation, Houston, Texas.

PY - 1987/1/26

Y1 - 1987/1/26

N2 - The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. α-Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3×10-4 mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer.

AB - The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. α-Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3×10-4 mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer.

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Effects of cyclosporine and α-difluoromethylornithine on the growth of mouse colon cancer in vitro

Abstract

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