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Tumor Response and Apoptosis of N1-S1 Rodent Hepatomas in Response to Intra-arterial and Intravenous Benzamide Riboside

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Abstract

Purpose

Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR.

Methods

A total of 106 N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40× magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test.

Results

Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P = 0.18); IA BR and saline (44.49 vs. 33.83%; P = 0.66); or IV BR and saline (1.52 vs. 193%; P = 0.18).

Conclusions

Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.

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Acknowledgments

This project was partially funded by a pilot grant and a clinical fellowship research grant from the Society of Interventional Radiology Foundation.

Conflict of interest

Dr. Jayaram holds U.S. patent 5902792 (International Class A61K 31/70 [20060101]) for a “Method of inducing apoptosis in cancer cells,” which covers the use of BR and its salts to cause cancer cell death. All other authors have nothing to disclose.

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Authors and Affiliations

  1. Imaging Institute and Department of Bioengineering, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA

    Gordon McLennan, Stacy L. Bennett & Seth Levitin

  2. Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China

    Shenghong Ju

  3. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA

    Andriy Babsky, Navin Bansal & Michelle L. Shorten

  4. University of Minnesota Center for Drug Design, Minneapolis, MN, USA

    Laurent Bonnac & Krystoff W. Panciewicz

  5. Department of Biochemistry, Indiana University and Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA

    Hiramagular N. Jayaram

Authors
  1. Gordon McLennan
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  2. Stacy L. Bennett
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  10. Hiramagular N. Jayaram
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Correspondence to Gordon McLennan.

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McLennan, G., Bennett, S.L., Ju, S. et al. Tumor Response and Apoptosis of N1-S1 Rodent Hepatomas in Response to Intra-arterial and Intravenous Benzamide Riboside. Cardiovasc Intervent Radiol 35, 645–652 (2012). https://doi.org/10.1007/s00270-011-0140-z

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  • DOI: https://doi.org/10.1007/s00270-011-0140-z

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