Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer
Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarb...
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MDPI AG
2018-03-01
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| Series: | Medical Sciences |
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| Online Access: | http://www.mdpi.com/2076-3271/6/1/24 |
| _version_ | 1819074897396105216 |
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| author | T. J. Thomas Thresia Thomas |
| author_facet | T. J. Thomas Thresia Thomas |
| author_sort | T. J. Thomas |
| collection | DOAJ |
| description | Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N1-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents. |
| first_indexed | 2024-12-21T18:16:49Z |
| format | Article |
| id | doaj.art-c4ca137942ca46bf93e4d372996b47ba |
| institution | Directory Open Access Journal |
| issn | 2076-3271 |
| language | English |
| last_indexed | 2024-12-21T18:16:49Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medical Sciences |
| spelling | doaj.art-c4ca137942ca46bf93e4d372996b47ba2022-12-21T18:54:39ZengMDPI AGMedical Sciences2076-32712018-03-01612410.3390/medsci6010024medsci6010024Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast CancerT. J. Thomas0Thresia Thomas1Department of Medicine, Rutgers Robert Wood Johnson Medical School and Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 675 Hoes Lane West, KTL Room N102, Piscataway, NJ 08854, USARetired from Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School and Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 675 Hoes Lane West, Piscataway, NJ 08854, USAPolyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N1-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents.http://www.mdpi.com/2076-3271/6/1/24polyaminesornithine decarboxylasepolyamine analogsspermidine/spermine N1-acetyl transferasespermine oxidasebis(ethyl)polyamine analogsbreast cancerMCF-7 cellstransgenic mice |
| spellingShingle | T. J. Thomas Thresia Thomas Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer Medical Sciences polyamines ornithine decarboxylase polyamine analogs spermidine/spermine N1-acetyl transferase spermine oxidase bis(ethyl)polyamine analogs breast cancer MCF-7 cells transgenic mice |
| title | Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer |
| title_full | Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer |
| title_fullStr | Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer |
| title_full_unstemmed | Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer |
| title_short | Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer |
| title_sort | cellular and animal model studies on the growth inhibitory effects of polyamine analogues on breast cancer |
| topic | polyamines ornithine decarboxylase polyamine analogs spermidine/spermine N1-acetyl transferase spermine oxidase bis(ethyl)polyamine analogs breast cancer MCF-7 cells transgenic mice |
| url | http://www.mdpi.com/2076-3271/6/1/24 |
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