Human prostatic carcinoma cell lines display altered regulation of polyamine transport in response to polyamine analogs and inhibitors

The Prostate
Z MiC W Porter

Abstract

The possibility was investigated that complex homeostatic mechanisms which maintain polyamine pools in prostate-derived tumors may differ from those which are typically seen in other tissues and tumors. Growth sensitivity and various regulatory responses were investigated in three human prostate carcinoma cell lines (LNCaP, DU145, and PC-3) treated with the inhibitor of S-adenosylmethionine decarboxylase CGP-48664 or the polyamine analog N1,N11-diethylnorspermine (DENSPM), both of which are currently undergoing phase I clinical trial. Prostate tumor cell lines were all similarly growth-inhibited by the inhibitor CGP-48664 (IC50 values, 1-5 microM at 72 hr), but varied considerably in their sensitivity to DENSPM. The rank-order for cell-line growth inhibition by the analog was DU145 > PC-3 > LNCaP, with IC50 values of 1, 30, and 1,000 microM, respectively. Both compounds depleted intracellular polyamine pools to levels which seemed sufficient to account for inhibition of cell growth. While polyamine enzyme regulatory responses to both CGP-48664 and DENSPM were typical of those seen in other cell types, regulation of polyamine transport differed distinctly. Based on Vmax determinations, LNCaP cells failed to upregulate transport ...Continue Reading

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Citations

May 7, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G BistulfiD J Smiraglia
Sep 13, 2011·Amino Acids·Rachelle R OlsenBruce R Zetter
Aug 17, 2005·Prostate Cancer and Prostatic Diseases·Y ZhangL Gong
Jun 20, 2001·The Journal of Eukaryotic Microbiology·C J BacchiM Wittner
Aug 2, 2013·NMR in Biomedicine·M Albert ThomasSteven S Raman
Jul 15, 2004·The Journal of Biological Chemistry·Kristin KeeCarl W Porter
May 1, 2021·International Journal of Molecular Sciences·Qiang PengChi-Fai Ng
Jul 11, 2000·Seminars in Cancer Biology·R G SchipperA A Verhofstad

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