This Article Full Text 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 McCloskey, D. E. Articles by Davidson, N. E. Search for Related Content PubMed PubMed Citation Articles by McCloskey, D. E. Articles by Davidson, N. E.

Effects of the Polyamine Analogues N¹ -Ethyl-N¹¹-((cyclopropyl)methyl)-4,8-diazaundecane and N¹-Ethyl-N¹¹-((cycloheptyl)methyl)-4,8- diazaundecane in Human Prostate Cancer Cells¹

The Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 [N. E. D., R. A. C.]; Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033 [D. E. M.]; and Wayne State University, Detroit, Michigan 48202 [P. M. W.]

The high levels of polyamines maintained in the prostate suggest that these compounds are important to prostate cell function and that disruption of polyamine metabolism may be an effective way to stop the growth of prostate cancer cells. The unsymmetrically alkylated polyamine analogues N¹-ethyl-N¹¹-((cyclopropyl)methyl)-4,8-diazaundecane (CPENSpm) and N¹-ethyl-N¹¹-((cycloheptyl)methyl)-4,8-diazaundecane (CHENSpm) have been shown pre-viously to have cytotoxic effects in breast and non-small cell lung cancer cells. We have now investigated the responses of three human prostate cancer cell lines, LNCaP, PC3, and Du145, to these polyamine analogues and to the symmetrically alkylated analogue N¹,N¹¹-bis(ethyl)norspermine (BE 3-3-3). The Du145 cell line, in which IC₅₀ values ranged from 0.65 to 0.8 µM, was the most sensitive to each of the polyamine analogues, although significant growth inhibition resulted in the other cell lines as well. CPENSpm and BE 3-3-3 but not CHENSpm caused significant decreases in the intracellular spermine and spermidine pools, although all three analogues accumulated to high levels in each of the cell lines. Spermidine/spermine N¹-acetyltransferase activity was induced 23–250-fold in response to CPENSpm and BE 3-3-3, but it was not affected by CHENSpm. None of the analogues had significant effects on the activities of ornithine decarboxylase or S-adenosylmethionine decarboxylase. Quantitation of DNA fragmentation indicative of programmed cell death (PCD) showed that both CPENSpm and CHENSpm were effective inducers of PCD in all three prostate cell lines. In contrast, BE 3-3-3 led to PCD only in LNCaP cells. The ability to induce PCD was the only parameter measured that correlated with cell line sensitivity to these polyamine analogues.

This article has been cited by other articles:

				D. L. Carlisle, W. L. Devereux, A. Hacker, P. M. Woster, and R. A. Casero Jr. Growth Status Significantly Affects the Response of Human Lung Cancer Cells to Antitumor Polyamine-Analogue Exposure Clin. Cancer Res., August 1, 2002; 8(8): 2684 - 2689. [Abstract] [Full Text] [PDF]

				K. R. Lawson, S. Marek, J. A. Linehan, P. M. Woster, R. A. Casero Jr., C. M. Payne, and E. W. Gerner Detoxification of the Polyamine Analogue N1-Ethyl-N11-[(cycloheptyl)methy]-4,8-diazaundecane (CHENSpm) by Polyamine Oxidase Clin. Cancer Res., May 1, 2002; 8(5): 1241 - 1247. [Abstract] [Full Text] [PDF]

				R. Riesenberg, A. Buchner, H. Pohla, and H. Lindhofer Lysis of Prostate Carcinoma Cells by Trifunctional Bispecific Antibodies ({{alpha}}EpCAM {{alpha}}CD3) J. Histochem. Cytochem., July 1, 2001; 49(7): 911 - 918. [Abstract] [Full Text] [PDF]

				D. E. McCloskey and A. E. Pegg Altered Spermidine/Spermine N1-Acetyltransferase Activity as a Mechanism of Cellular Resistance to Bis(ethyl)polyamine Analogues J. Biol. Chem., September 8, 2000; 275(37): 28708 - 28714. [Abstract] [Full Text] [PDF]