Cancer, polyamines

The polyamines putrescine, cadaverine, spermidine, and spermine, which are seen at elevated levels in some victims of cancer, were separated on a Technicon (The Technicon Company Chauncey, NY) TSM Amino Acid Analyzer packed with an 8% divinylbenzene-co-polystyrene sulfonated resin with post-column ninhydrin detection.111 Amines such as ethanolamine, noradrenaline, hexamethylene diamine, methoxytryptamine, spermine, and spermidine were separated from amino acids on a DC-4A cation exchange resin.112 A similar approach, using a Beckman Model 121M amino acid analyzer equipped with an AA-20 column, was also successful.113 A Polyamin-pak strong cation exchange column (JASCO) was eluted with a citrate buffer for the detection of putrescene, spermine, cadaverine, and 1,5-diaminohex-ane from rat thymus.114 A post-column o-phthaldehyde detection system was used. 

Polyamines and their ammonium salts have been of interest because they are known to have potential applications as chelating agents (1-3), ion exchange resins (4-6), flocculants (7,8), and other industrial uses (9). Recent biomedical applications have constituted another important use of polymeric amines they have been investigated for use as biocompatable materials, polymeric drugs, immobilization of enzymes, cell-culture substratum and cancer chemotherapeutic agents (10-12). 

Pretreatment of rats with difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, prior to exposure to a tremorigenic dose of chlordecone, also resulted in inhibition of the tremor (Tilson et al. 1986b). DFMO was more effective if given 5 hours prior to the chlordecone than if given 24 hours prior to exposure. The DFMO was ineffective if given 19 hours after chlordecone exposure. These results suggest an interaction of the polyamine synthetic pathway with tremors produced by chlordecone. The mechanism of the interaction is unclear but may involve effects of polyamines on intracellular calcium homeostasis. Persons being treated with DFMO for cancer or protozoal infections would be likely to have reduced tremor severity after exposure to chlordecone. 

While GC has not been used extensively to analyze polyamines, a review in 2002 comprehensively covers useful methods (Teti et al., 2002) and a review in 2001 includes specific methods for various polyamines that are used to monitor cancer remission (Khuhawar and Qureshi, 2001). Using activated Permutit for cleanup and heptafluorobutyric anhydride for derivatization, sensitivities of 0.02-0.1 pmol were achieved for commonly analyzed polyamines using GC-ECD and human plasma samples (Teti et al., 2002). NPD also has utility because low detection limits are easily attained (Teti et al., 2002). PFB derivatives have shown some utility with GC-ECD (Coutts and Baker, 1982 Clements et al., 2004), and heptafluorobutryic anhydride with GC-ECD has also been used with success for analysis in human blood samples (Fujihara et al., 1983). 

Khuhawar MY, Qureshi GA. 2001. Polyamines as cancer markers applicable separation methods. J Chromatogr B... 

S.2.3.3 Treatment of Trypanosomiasis The difluoromethylornithine (DFMO), eflomithine is a mechanism-based inhibitor of ornithine decarboxylase— a pyridoxal-dependent key enzyme of the polyamine s biosynthesis from ornithine. Fluorine atoms are essential for the inhibition process (cf. Chapter 7). Eflornithine was first clinically developed for cancer, but its development has been abandoned for this indication. The activity of eflornithine on trypanosomes was then discovered. Now, despite its very low bioavailability, eflornithine is the best therapy for sleeeping sickness (trypanosomiasis)—in particular, at the cerebral stage—due to Trypanosoma brucei gambiense parasite. Eflornithine is registered with orphan drug status and is distributed by the WHO. 

Wang JY, Casero RA, Jr. (2006) Polyamine Cell Signaling Physiology, Pharmacology, and Cancer Research. Humana Press Inc., Totowa, NJ... 

Fiorina VJ, Dubois RJ, Brynes S (1978) Ferrocenyl polyamines as agents for chemoimmu-notherapy of cancer. J Med Chem 21 393-395... 

Hobbs CA, Gilmour SK (2006) In polyamine cell signaling Physiology, Phamacology, and Cancer Research. Humana Press, Totowa, p 75... 

Camesecchi, S. Schneider, Y. Lazarus, S.A. Coehlo, D. Gosse, F. Raul, F. 2002. Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells. Cancer Lett. 175 147-155. 

Pegg, A.E. Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Res. 1988, 48, 759. 

Hair may also be an important tool for the diagnosis and monitoring of various disease states. For example, the concentrations of polyamines (e.g., putrescine, spermidine, and spermine) in the hair may be helpful in diagnosing and assessing disease activity in women with cervical or ovarian cancer. Assessing the level of polyamines in the hair shaft is preferred to measuring them in plasma and urine because the polyamine levels can vary during the day in plasma and urine. Increased levels of porphyrins in hair have been detected in patients with porphyria... 

Choi MH, Kim KR, Kim YT, and Chung BC (2001) Increased polyamine concentrations in the hair of cancer patients. Clinical Chemistry 47 143-144. 

The converged absorption component shape spectrum (top panel (i)) and total absorption shape spectrum (lower panel (ii)) for prosfafe cancer between 2.40 and 3.70 ppm at Np = 800 are compared in Figure 6.26. Strikingly, the serrated peaks on the total shape spectrum only suggest the number of underlying resonances. The converged componenf specfrum is essential to visualize the actual number and structure of resonances. For example, from the small polyamine peaks, it would be difficult to know that there are actually two components. 

Normal glandular and normal stromal prostate show markedly different spectral patterns. Most notably, the resonances are much smaller in the stromal tissue. Lactate at 1.33 ppm and creatine at 3.04 ppm are the most prominent structures. The lactate peaks at 1.33 and 4.12 ppm are larger in the prostate cancer spectra compared with the two normal prostate tissues. The choline components at 3.21-3.24 ppm (i.e., total choline) are more abundant than creatine at 3.04 ppm. The spectrum for prostate cancer differs most clearly from that of normal glandular prostate, particularly in the spectrum for prostate cancer the citrate doublet peaks and the two polyamine resonances are much smaller than the components of choline. 

Thompson HJ, Herbst EJ, Meeker LD. 1986. Chemoprevention of mammary carcinogenesis A comparative review of the efficacy of a polyamine antimetabolite, retinoids, and selenium. J Natl Cancer Inst 77 595-598. 

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