This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Igarashi, K. Articles by Shirahata, A. Search for Related Content PubMed PubMed Citation Articles by Igarashi, K. Articles by Shirahata, A.

Inhibition of the Growth of Various Human and Mouse Tumor Cells by 1,15-Bis(ethylamino)-4,8,12-triazapentadecane¹

Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263 [K. I., Y. H., T. S., K. Ka.]; Research Laboratories, Pharmaceutical Group, Nippon Kayaku Co., Ltd., 3-12 Shimo, 3-Chome, Kita-ku, Tokyo 115 [K. Ko., H. E.]; and Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-02 [A. S.], Japan

Effects of 1,15-bis(ethylamino)-4,8,12-triazapentadecane (BE3333), the least toxic bis(ethyl)pentaamine, on the growth of tumor cells were studied in in vitro systems and with tumor xenografts in mice. BE3333 suppressed ornithine decarboxylase and S-adenosylmethionine decarboxylase, induced spermidine/spermine N¹-acetyltransferase, and thus decreased the amount of polyamines. BE3333 accumulated in cells at a concentration 3–5-fold that of spermine in control cells through the polyamine transport system. The accumulated BE3333 inhibited protein synthesis, especially mitochondrial protein synthesis, and decreased the amount of ATP. The inhibition of protein synthesis was correlated with the subsequent inhibition of cell growth. BE3333 showed inhibitory effects in in vitro systems against the growth of mouse FM3A mammary carcinoma cells, human SW480 and SW620 colon tumor cells, Lu-65A and A549 lung tumor cells, MCF-7 breast tumor cells, and MALME-3M and A375 melanoma cells at a range of 0.5–10 µM. Intravenous (30 mg/kg) or i.p. (50 mg/kg) daily injections of BE3333 for 5 or 7 days greatly suppressed the growth of human colon tumor SW620 xenotransplanted into nude mice. Similar antitumor activity was obtained with continuous infusion of BE3333 into the peritoneal cavity (80 mg/kg), but not with p.o. administration (200 mg/kg). BE3333 also showed inhibitory effects against the growth of lung tumors (Lu-65, Lx-1, Lc-1, and Lu-61), stomach tumors (Sc-6 and St-15), and melanoma (SEKI) xenotransplanted into nude mice. The results indicate that BE3333 is effective against both rapid- and slow-growing tumors, with reasonable short-term host toxicity.

¹ This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture (Japan) and by research aid from the Research Foundation for Pharmaceutical Sciences.

² To whom requests for reprints should be addressed.

Received 12/16/94. Accepted 4/17/95.

This article has been cited by other articles:

				G. Mantovani, C. Madeddu, A. Maccio, G. Gramignano, M. R. Lusso, E. Massa, G. Astara, and R. Serpe Cancer-Related Anorexia/Cachexia Syndrome and Oxidative Stress: An Innovative Approach beyond Current Treatment Cancer Epidemiol. Biomarkers Prev., October 1, 2004; 13(10): 1651 - 1659. [Abstract] [Full Text] [PDF]

				M. Saminathan, T. Thomas, A. Shirahata, C. K. S. Pillai, and T. J. Thomas Polyamine structural effects on the induction and stabilization of liquid crystalline DNA: potential applications to DNA packaging, gene therapy and polyamine therapeutics Nucleic Acids Res., September 1, 2002; 30(17): 3722 - 3731. [Abstract] [Full Text] [PDF]

				V. S. Raj, H. Tomitori, M. Yoshida, A. Apirakaramwong, K. Kashiwagi, K. Takio, A. Ishihama, and K. Igarashi Properties of a Revertant of Escherichia coli Viable in the Presence of Spermidine Accumulation: Increase in L-Glycerol 3-Phosphate J. Bacteriol., August 1, 2001; 183(15): 4493 - 4498. [Abstract] [Full Text] [PDF]

				P. Aich, T. J. Thomas, and J. S. Lee The role of polyamines, Na+ and K+ in the formation of triple helices between purine oligonucleotides and the promoter region of the human c-src proto-oncogene Nucleic Acids Res., June 15, 2000; 28(12): 2307 - 2310. [Abstract] [Full Text] [PDF]

				A. Ushmorov, V. Hack, and W. Droge Differential Reconstitution of Mitochondrial Respiratory Chain Activity and Plasma Redox State by Cysteine and Ornithine in a Model of Cancer Cachexia Cancer Res., July 1, 1999; 59(14): 3527 - 3534. [Abstract] [Full Text] [PDF]

				M. Fogel-Petrovic, D. L. Kramer, S. Vujcic, J. Miller, J. S. Mcmanis, R. J. Bergeron, and C. W. Porter Structural Basis for Differential Induction of Spermidine/Spermine N1-Acetyltransferase Activity by Novel Spermine Analogs Mol. Pharmacol., July 1, 1997; 52(1): 69 - 74. [Abstract] [Full Text]

				K. Kashiwagi, S. Shibuya, H. Tomitori, A. Kuraishi, and K. Igarashi Excretion and Uptake of Putrescine by the PotE Protein in Escherichia coli J. Biol. Chem., March 7, 1997; 272(10): 6318 - 6323. [Abstract] [Full Text] [PDF]