Inhibition of tumor growth by targeted toxins in mice is dramatically improved by saponinum album in a synergistic way.
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.
Bachran
Christopher
C
Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin , Berlin, Germany. christopher.bachran@charite.de
Dürkop
Horst
H
Sutherland
Mark
M
Bachran
Diana
D
Müller
Christian
C
Weng
Alexander
A
Melzig
Matthias F
MF
Fuchs
Hendrik
H
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000494:pharmacology; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000076985:Saporins; D016896:Treatment Outcome; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects
D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D012503:Saponins; D014315:Triterpenes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000076985:Saporins