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 Casero, R. A. Articles by Libby, P. R. Search for Related Content PubMed PubMed Citation Articles by Casero, R. A., Jr. Articles by Libby, P. R.

Differential Induction of Spermidine/Spermine N¹-Acetyltransferase in Human Lung Cancer Cells by the Bis(ethyl)polyamine Analogues¹

The Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 [R. A. C., P. C., S. J. E.]; The Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263 [C. W. P., P. R. L.]; and The Department of Medicinal Chemistry, J. Hillis Miller Health Center, University of Florida, Gainesville, Florida 32610 [R. J. B.]

We have investigated the induction of an important polyamine metabolic enzyme, spermidine/spermine N¹-acetyltransferase, in two human lung cancer cell lines which respond differently to treatment with the bis(ethyl)polyamine analogues. The human small cell lung carcinoma line NCI H82 has previously been shown to be minimally affected by treatment with these analogues, whereas the large cell undifferentiated lung carcinoma line, NCI H157, responds in a rapid cytotoxic manner (R. A. Casero, Jr., S. J. Ervin, P. Celano, S. B. Baylin, and R. J. Bergeron, Cancer Res., 49: 639–643, 1989). The mechanisms underlying the differential response are unknown. In the responsive NCI H157 cells, the bis(ethyl)polyamines were found to induce spermidine/spermine N¹-acetyltransferase in a time- and dose-dependent manner to maximum levels >1700-fold over baseline. By contrast, the unresponsive NCI H82 cells exhibit minimal induction of spermidine/spermine N¹-acetyltransferase to <7-fold increase after bis(ethyl)polyamine treatment, regardless of time or concentration examined. The results of the current study suggest that the differential induction of this key enzyme, which is rate limiting in the back conversion pathway of polyamine metabolism, may play a role in determining cell specific sensitivity to the bis(ethyl)polyamine analogues.

¹ This work was supported by NIH Grants CA37606 and CA47492.

² To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center Laboratories, 424 North Bond Street, Baltimore, MD 21231.

Received 2/ 1/89. Revised 4/ 3/89. Accepted 4/13/89.

This article has been cited by other articles:

				A. E. Pegg Spermidine/spermine-N1-acetyltransferase: a key metabolic regulator Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E995 - E1010. [Abstract] [Full Text] [PDF]

				D. L. Kramer, P. Diegelman, J. Jell, S. Vujcic, S. Merali, and C. W. Porter Polyamine Acetylation Modulates Polyamine Metabolic Flux, a Prelude to Broader Metabolic Consequences J. Biol. Chem., February 15, 2008; 283(7): 4241 - 4251. [Abstract] [Full Text] [PDF]

				N. J. Butcher, G. M. Broadhurst, and R. F. Minchin Polyamine-dependent Regulation of Spermidine-Spermine N1-Acetyltransferase mRNA Translation J. Biol. Chem., September 28, 2007; 282(39): 28530 - 28539. [Abstract] [Full Text] [PDF]

				N. Babbar and R. A. Casero Jr. Tumor Necrosis Factor-{alpha} Increases Reactive Oxygen Species by Inducing Spermine Oxidase in Human Lung Epithelial Cells: A Potential Mechanism for Inflammation-Induced Carcinogenesis Cancer Res., December 1, 2006; 66(23): 11125 - 11130. [Abstract] [Full Text] [PDF]

				N. Babbar, A. Hacker, Y. Huang, and R. A. Casero Jr. Tumor Necrosis Factor {alpha} Induces Spermidine/Spermine N1-Acetyltransferase through Nuclear Factor {kappa}Bin Non-small Cell Lung Cancer Cells J. Biol. Chem., August 25, 2006; 281(34): 24182 - 24192. [Abstract] [Full Text] [PDF]

				Y. Wang and R. A. Casero Jr. Mammalian Polyamine Catabolism: A Therapeutic Target, a Pathological Problem, or Both? J. Biochem., January 1, 2006; 139(1): 17 - 25. [Abstract] [Full Text] [PDF]

				A. Pledgie, Y. Huang, A. Hacker, Z. Zhang, P. M. Woster, N. E. Davidson, and R. A. Casero Jr. Spermine Oxidase SMO(PAOh1), Not N1-Acetylpolyamine Oxidase PAO, Is the Primary Source of Cytotoxic H2O2 in Polyamine Analogue-treated Human Breast Cancer Cell Lines J. Biol. Chem., December 2, 2005; 280(48): 39843 - 39851. [Abstract] [Full Text] [PDF]

				J. M. Tucker, J. T. Murphy, N. Kisiel, P. Diegelman, K. W. Barbour, C. Davis, M. Medda, L. Alhonen, J. Janne, D. L. Kramer, et al. Potent Modulation of Intestinal Tumorigenesis in Apcmin/+ Mice by the Polyamine Catabolic Enzyme Spermidine/Spermine N1-acetyltransferase Cancer Res., June 15, 2005; 65(12): 5390 - 5398. [Abstract] [Full Text] [PDF]

				K. Kee, B. A. Foster, S. Merali, D. L. Kramer, M. L. Hensen, P. Diegelman, N. Kisiel, S. Vujcic, R. V. Mazurchuk, and C. W. Porter Activated Polyamine Catabolism Depletes Acetyl-CoA Pools and Suppresses Prostate Tumor Growth in TRAMP Mice J. Biol. Chem., September 17, 2004; 279(38): 40076 - 40083. [Abstract] [Full Text] [PDF]

				A. P. Gobert, Y. Cheng, M. Akhtar, B. D. Mersey, D. R. Blumberg, R. K. Cross, R. Chaturvedi, C. B. Drachenberg, J.-L. Boucher, A. Hacker, et al. Protective Role of Arginase in a Mouse Model of Colitis J. Immunol., August 1, 2004; 173(3): 2109 - 2117. [Abstract] [Full Text] [PDF]

				S. Hector, C. W. Porter, D. L. Kramer, K. Clark, J. Prey, N. Kisiel, P. Diegelman, Y. Chen, and L. Pendyala Polyamine catabolism in platinum drug action: Interactions between oxaliplatin and the polyamine analogue N1,N11-diethylnorspermine at the level of spermidine/spermine N1-acetyltransferase Mol. Cancer Ther., July 1, 2004; 3(7): 813 - 822. [Abstract] [Full Text] [PDF]

				K. Kee, S. Vujcic, S. Merali, P. Diegelman, N. Kisiel, C. T. Powell, D. L. Kramer, and C. W. Porter Metabolic and Antiproliferative Consequences of Activated Polyamine Catabolism in LNCaP Prostate Carcinoma Cells J. Biol. Chem., June 25, 2004; 279(26): 27050 - 27058. [Abstract] [Full Text] [PDF]

				A. C. Wolff, D. K. Armstrong, J. H. Fetting, M. K. Carducci, C. D. Riley, J. F. Bender, R. A. Casero Jr., and N. E. Davidson A Phase II Study of the Polyamine Analog N1,N11-Diethylnorspermine (DENSpm) Daily for Five Days Every 21 Days in Patients with Previously Treated Metastatic Breast Cancer Clin. Cancer Res., December 1, 2003; 9(16): 5922 - 5928. [Abstract] [Full Text] [PDF]

				D. E. McCloskey and A. E. Pegg Properties of the Spermidine/Spermine N1-Acetyltransferase Mutant L156F That Decreases Cellular Sensitivity to the Polyamine Analogue N1, N11-Bis(ethyl)norspermine J. Biol. Chem., April 11, 2003; 278(16): 13881 - 13887. [Abstract] [Full Text] [PDF]

				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. Niiranen, M. Pietila, T. J. Pirttila, A. Jarvinen, M. Halmekyto, V.-P. Korhonen, T. A. Keinanen, L. Alhonen, and J. Janne Targeted Disruption of Spermidine/Spermine N1-Acetyltransferase Gene in Mouse Embryonic Stem Cells. EFFECTS ON POLYAMINE HOMEOSTASIS AND SENSITIVITY TO POLYAMINE ANALOGUES J. Biol. Chem., July 5, 2002; 277(28): 25323 - 25328. [Abstract] [Full Text] [PDF]

				H. A. Hahm, D. S. Ettinger, K. Bowling, B. Hoker, T. L. Chen, Y. Zabelina, and R. A. Casero Jr. Phase I Study of N1,N11-Diethylnorspermine in Patients with Non-Small Cell Lung Cancer Clin. Cancer Res., March 1, 2002; 8(3): 684 - 690. [Abstract] [Full Text] [PDF]

				D. L. Kramer, B.-D. Chang, Y. Chen, P. Diegelman, K. Alm, A. R. Black, I. B. Roninson, and C. W. Porter Polyamine Depletion in Human Melanoma Cells Leads to G1 Arrest Associated with Induction of p21WAF1/CIP1/SDI1, Changes in the Expression of p21-regulated Genes, and a Senescence-like Phenotype Cancer Res., November 1, 2001; 61(21): 7754 - 7762. [Abstract] [Full Text] [PDF]

				Y. Wang, W. Devereux, P. M. Woster, T. M. Stewart, A. Hacker, and R. A. Casero Jr. Cloning and Characterization of a Human Polyamine Oxidase That Is Inducible by Polyamine Analogue Exposure Cancer Res., July 1, 2001; 61(14): 5370 - 5373. [Abstract] [Full Text] [PDF]

				N. Yarlett, M. P. Martinez, B. Goldberg, D. L. Kramer, and C. W. Porter Dependence of Trichomonas vaginalis upon polyamine backconversion Microbiology, October 1, 2000; 146(10): 2715 - 2722. [Abstract] [Full Text]

				D. E. McCloskey, P. M. Woster, R. A. Casero Jr., and N. E. Davidson 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 Cells Clin. Cancer Res., January 1, 2000; 6(1): 17 - 23. [Abstract] [Full Text]

				Y. Wang, W. Devereux, T. M. Stewart, and R. A. Casero Jr. Cloning and Characterization of Human Polyamine-modulated Factor-1, a Transcriptional Cofactor That Regulates the Transcription of the Spermidine/Spermine N1-Acetyltransferase Gene J. Biol. Chem., July 30, 1999; 274(31): 22095 - 22101. [Abstract] [Full Text] [PDF]

				E. W. Gabrielson, A. E. Pegg, and R. A. Casero Jr. The Induction of Spermidine/Spermine N1-Acetyltransferase (SSAT) Is a Common Event in the Response of Human Primary Non-Small Cell Lung Carcinomas to Exposure to the New Antitumor Polyamine Analogue N1,N11-Bis(ethyl)norspermine1 Clin. Cancer Res., July 1, 1999; 5(7): 1638 - 1641. [Abstract] [Full Text] [PDF]

				L. Alhonen, M. Pietilä, M. Halmekytö, D. L. Kramer, J. Jänne, and C. W. Porter Transgenic Mice with Activated Polyamine Catabolism due to Overexpression of Spermidine/Spermine N1-Acetyltransferase Show Enhanced Sensitivity to the Polyamine Analog, N1,N11-Diethylnorspermine Mol. Pharmacol., April 1, 1999; 55(4): 693 - 698. [Abstract] [Full Text]

				D. E. McCloskey, C. S. Coleman, and A. E. Pegg Properties and Regulation of Human Spermidine/Spermine N1-Acetyltransferase Stably Expressed in Chinese Hamster Ovary Cells J. Biol. Chem., March 5, 1999; 274(10): 6175 - 6182. [Abstract] [Full Text] [PDF]

				D. L. Kramer, S. Vujcic, P. Diegelman, J. Alderfer, J. T. Miller, J. D. Black, R. J. Bergeron, and C. W. Porter Polyamine Analogue Induction of the p53-p21WAF1/CIP1-Rb Pathway and G1 Arrest in Human Melanoma Cells Cancer Res., March 1, 1999; 59(6): 1278 - 1286. [Abstract] [Full Text] [PDF]

				Y. Wang, L. Xiao, A. Thiagalingam, B. D. Nelkin, and R. A. Casero Jr. The Identification of a Cis-element and a Trans-acting Factor Involved in the Response to Polyamines and Polyamine Analogues in the Regulation of the Human Spermidine/Spermine N1-Acetyltransferase Gene Transcription J. Biol. Chem., December 18, 1998; 273(51): 34623 - 34630. [Abstract] [Full Text] [PDF]

				K. Otani, Y. Yano, T. Hasuma, T. Arakawa, K. Kobayashi, I. Matsui-Yuasa, and S. Otani Polyamine metabolism of rat gastric mucosa after oral administration of hypertonic sodium chloride solution Am J Physiol Gastrointest Liver Physiol, February 1, 1998; 274(2): G299 - G305. [Abstract] [Full Text] [PDF]

				L. Alhonen, A. Karppinen, M. Uusi-Oukari, S. Vujcic, V.-P. Korhonen, M. Halmekyto, D. L. Kramer, R. Hines, J. Janne, and C. W. Porter Correlation of Polyamine and Growth Responses to N1,N11-Diethylnorspermine in Primary Fetal Fibroblasts Derived from Transgenic Mice Overexpressing Spermidine/Spermine N1-Acetyltransferase J. Biol. Chem., January 23, 1998; 273(4): 1964 - 1969. [Abstract] [Full Text] [PDF]

				M. Pietila, L. Alhonen, M. Halmekyto, P. Kanter, J. Janne, and C. W. Porter Activation of Polyamine Catabolism Profoundly Alters Tissue Polyamine Pools and Affects Hair Growth and Female Fertility in Transgenic Mice Overexpressing Spermidine/Spermine N1-Acetyltransferase J. Biol. Chem., July 25, 1997; 272(30): 18746 - 18751. [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]

				C. S. Coleman and A. E. Pegg Proteasomal Degradation of Spermidine/Spermine N1-Acetyltransferase Requires the Carboxyl-terminal Glutamic Acid Residues J. Biol. Chem., May 2, 1997; 272(18): 12164 - 12169. [Abstract] [Full Text] [PDF]

				L. Lu, K. A. Berkey, and R. A. Casero Jr. RGFGIGS Is an Amino Acid Sequence Required for Acetyl Coenzyme A Binding and Activity of Human Spermidine/Spermine N1Acetyltransferase J. Biol. Chem., August 2, 1996; 271(31): 18920 - 18924. [Abstract] [Full Text] [PDF]

				S. Vujcic, M. Halmekyto, P. Diegelman, G. Gan, D. L. Kramer, J. Janne, and C. W. Porter Effects of Conditional Overexpression of Spermidine/Spermine N1-Acetyltransferase on Polyamine Pool Dynamics, Cell Growth, and Sensitivity to Polyamine Analogs J. Biol. Chem., December 1, 2000; 275(49): 38319 - 38328. [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]