Inhibition of tumor growth by targeted toxins in mice is dramatically improved by saponinum album in a synergistic way.

Abstract

The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice bearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters; histologic analyses and antibody responses were only moderate and usually reversible.

• Authors: Christopher Bachran, Horst Dürkop, Mark Sutherland, Diana Bachran, Christian Müller, Alexander Weng, Matthias F Melzig, Hendrik Fuchs
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 32 Issue 7 Pg. 713-25 (Sep 2009) ISSN: 1537-4513 [Electronic] United States
• PMID: 19561537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunotoxins
• Ribosome Inactivating Proteins, Type 1
• Saponins
• Triterpenes
• Epidermal Growth Factor
• ErbB Receptors
• Saporins

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Synergism
• Epidermal Growth Factor (administration & dosage, pharmacology)
• ErbB Receptors (genetics, metabolism)
• Female
• Humans
• Immunotoxins (administration & dosage, chemistry, pharmacology)
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Ribosome Inactivating Proteins, Type 1 (administration & dosage, pharmacology)
• Saponins (administration & dosage, chemistry, pharmacology)
• Saporins
• Treatment Outcome
• Triterpenes (administration & dosage, chemistry, pharmacology)
• Tumor Burden (drug effects)