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 grow...

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Bibliographic Details
Published in:International journal of cancer 2010-09, Vol.127 (6), p.1453-1461
Main Authors: Bachran, Diana, Schneider, Stefanie, Bachran, Christopher, Urban, Romy, Weng, Alexander, Melzig, Matthias F., Hoffmann, Corinna, Kaufmann, Andreas M., Fuchs, Hendrik
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line, Tumor
Cnidarian Venoms - toxicity
Enzyme-Linked Immunosorbent Assay
epidermal growth factor
Female
Female genital diseases
Gynecology. Andrology. Obstetrics
Humans
immunotherapy
immunotoxin
Medical sciences
Mice
Receptor, Epidermal Growth Factor - metabolism
saponin
Saponins - pharmacology
saporin
targeted tumor therapy
Tumors
Uterine Cervical Neoplasms - pathology
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Summary: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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.25123