Cationized Bowman-Birk protease inhibitor as a targeted cancer chemopreventive agent.

Abstract

The conjugate of the Bowman-Birk inhibitor (BBI) with poly(D-lysine) (PDL-ss-BBI) has been suggested as a lung-targeted anti-carcinogenic agent. The authors demonstrate that PDL-ss-BBI, given i.p., reduces the tumor number in the lungs of 3-methylcholanthrene treated mice (61-71% compared to control group) in a dose-dependent manner, but is toxic to the treated animals at a high dosage. In order to develop a better lung-targeted anti-carcinogenic agent, spermine-conjugated BBI (spermine-BBI) was synthesized by coupling BBI to spermine through amide bonds using a carbodiimide-mediated reaction. Results from in vitro transformation assays demonstrated that spermine-BBI was at least as effective as BBI in reducing the transformation yield in C3H10T1/2 cells. When injected intravenously into mice [125I]spermine-BBI accumulated to a greater extent in the lungs and the liver compared to BBI. The in vitro cytotoxicity of spermine-BBI in C3H10T1/2 cells was 30-fold less than that of PDL-ss-BBI. These results suggest that spermine-BBI is likely to be an improved cancer chemopreventive agent compared to BBI or PDL-ss-BBI.

• Authors: H Ekrami, A R Kennedy, H Witschi, W C Shen
• Journal: Journal of drug targeting (J Drug Target) Vol. 1 Issue 1 Pg. 41-9 ( 1993) ISSN: 1061-186X [Print] England
• PMID: 8069543 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Trypsin Inhibitor, Bowman-Birk Soybean
• Polylysine
• Spermine
• Methylcholanthrene
• Chymotrypsin

Topics

• Animals
• Anticarcinogenic Agents (administration & dosage, chemistry, pharmacology)
• Body Weight (drug effects)
• Cell Survival (drug effects)
• Chromatography, Gel
• Chymotrypsin (antagonists & inhibitors)
• Injections, Intravenous
• Lung Neoplasms (chemically induced, pathology, prevention & control)
• Male
• Methylcholanthrene
• Mice
• Mice, Inbred A
• Mice, Inbred BALB C
• Polylysine (chemistry, pharmacology)
• Spermine (chemistry, pharmacology)
• Tissue Distribution
• Trypsin Inhibitor, Bowman-Birk Soybean (administration & dosage, chemistry, pharmacology)
• Tumor Cells, Cultured