Epidermal growth factor receptor expression affects the efficacy of the combined application of saponin and a targeted toxin on human cervical carcinoma cells.
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.
Bachran
Diana
D
Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Schneider
Stefanie
S
Bachran
Christopher
C
Urban
Romy
R
Weng
Alexander
A
Melzig
Matthias F
MF
Hoffmann
Corinna
C
Kaufmann
Andreas M
AM
Fuchs
Hendrik
H
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*
D003064:Cnidarian Venoms; D012503:Saponins; D066246:ErbB Receptors