Antitumor effects of bis(ethyl)polyamine analogs on mammary tumor development in FVB/NTgN (MMTVneu) transgenic mice.
We studied the therapeutic potential of two polyamine analogs on breast cancer using FVB/NTgN (MMTVneu), a transgenic mouse model with neu/erb-B2 oncogene overexpression. Treatment was initiated at 31 weeks of age with bis(ethyl)norspermine (BE333) and its higher homolog, BE3333 as i.p. injections once weekly. There was a 40% reduction in the average number of tumors per mouse in both treatment groups, by 10 weeks of treatment. BE3333-treated mice had 70-75% lower tumor volume than controls. Spermidine/spermine acetyl transferase activity was significantly higher in tumor tissues and kidneys of treated animals, whereas polyamine levels were lower than controls. Beneficial effects were also evident from the mortality rates in control and treatment groups. Our results suggest a potential use of selected bis(ethyl) polyamine analogs as antitumor agents in breast cancer.
Shah
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Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903, USA.
Antony
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Haddad
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Amenta
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Shirahata
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Thomas
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Thomas
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D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015317:Biogenic Polyamines / Q000032:analysis; D005260:Female; D018734:Genes, erbB-2 / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008822:Mice, Transgenic; D011073:Polyamines / Q000627:therapeutic use*; D013096:Spermine / Q000031:analogs & derivatives*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D011073:Polyamines; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C094172:1,15-bis(ethylamino)-4,8,12-triazapentadecane; C059685:N(1),N(11)-diethylnorspermine