title: Epidermal growth factor receptor expression affects the efficacy of the combined application of saponin and a targeted toxin on human cervical carcinoma cells.
abstract: Cervical cancer is the second most common cancer in women worldwide. Targeting the epidermal growth factor receptor (EGFR) is a very promising approach since it is overexpressed in about 90% of cervical tumors. Here, we quantified the toxic effect of SE, a targeted toxin consisting of epidermal growth factor (EGF) as targeting moiety and the plant toxin saporin-3, on 3 common human cervical carcinoma cell lines (HeLa, CaSki and SiHa) and recently established lines (PHCC1 and PHCC2) from 2 different individuals. A human melanocytic and a mouse cell line served as negative control. Additionally, we combined SE with saponinum album, a saponin composite from Gypsophila paniculata, which exhibited synergistic properties in previous studies. The cell lines, except for SiHa cells, revealed high sensitivity to SE with 50% cell survival in the range of 5-24.5 nM. The combination with saponin resulted in a remarkable enhancement of cytotoxicity with enhancement factors ranging from 9,000-fold to 2,500,000-fold. The cytotoxicity of SE was clearly target receptor specific since free EGF blocks the effect and saporin-3 alone was considerably less toxic. For all cervical carcinoma cell lines, we evinced a clear correlation between EGFR expression and SE sensitivity. Our data indicate a potential use of targeted toxins for the treatment of cervical cancer. In particular, the combination with saponins is a promising approach since efficacy is drastically improved.
authors.affiliation: Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Bachran
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schneider
authors.forename: Christopher
authors.initials: C
authors.lastname: Bachran
authors.forename: Romy
authors.initials: R
authors.lastname: Urban
authors.forename: Alexander
authors.initials: A
authors.lastname: Weng
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Melzig
authors.forename: Corinna
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003064:Cnidarian Venoms / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D012503:Saponins / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D003064:Cnidarian Venoms; D012503:Saponins; D066246:ErbB Receptors