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Antitumor effects ofN-alkylated polyamine analogues in human pancreatic adenocarcinoma models

  • Original Articles
  • Polyamine Analogues, Pancreatic Adenocarcinoma, Polyamine Biosynthesis, Animal Tumor Models
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Summary

Adenocarcinoma of the pancreas presents a formidable challenge both experimentally and clinically, whereby effective anticancer therapy is lacking. We have recently explored a relatively new class of antitumor agents in pancreatic cancer cell lines and have found the bis-ethyl derivatives of spermine to show considerable promise. In the present paper, we report the results of in vivo studies demonstrating the antitumor activity of two of theseN-alkylated analogues,N 1,N 14-bis(ethyl)norspermine (BENSPM) in athymic (nude) mouse xenografts of two human pancreatic ductal adenocarcinoma cell lines, PANC-1 (poorly differentiated) and BxPC-3 (moderately well-differentiated). BENSPM was found to exert greater antitumor activity in vivo than either BEHSPM or other conventional agents, largely because higher doses could be given due to its lower toxicity to mice. BENSPM shows greater activity than any other agent we have thus far tested against our pancreatic-cancer models. Optimal schedules of administration have yet to be determined. Nevertheless, of the analogues tested, BENSPM presently appears to be the analogue of choice for further development.

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Authors and Affiliations

  1. Department of Medicine, Medical College of Georgia and Augusta VA Medical Center, 30910, Augusta, GA, USA

    Barbara K. Chang (Associate Chief Staff/Education (141-U) & Yayun Liang

  2. Grace Cancer Drug Center, Roswell Park Memorial Institute, 14263, Buffalo, NY, USA

    Carl W. Porter

  3. Department of Medicinal Chemistry, J. Hillis Miller Health Center, University of Florida, 32610, Gainesville, FL, USA

    Raymond J. Bergeron

Authors
  1. Barbara K. Chang
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  2. Raymond J. Bergeron
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  3. Carl W. Porter
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  4. Yayun Liang
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Additional information

This investigation was supported by grant CH-468 from the American Cancer Society, by grant CA-37 606 from the National Cancer Institute, Department of Health and Human Services, and by the Department of Veterans Affairs Medical Research Service

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Chang, B.K., Bergeron, R.J., Porter, C.W. et al. Antitumor effects ofN-alkylated polyamine analogues in human pancreatic adenocarcinoma models. Cancer Chemother. Pharmacol. 30, 179–182 (1992). https://doi.org/10.1007/BF00686308

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  • DOI: https://doi.org/10.1007/BF00686308

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