Abstract
Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing A431 and TE-8 human squamous carcinoma cells with an IC50 of 2 x 10-7 M and 10-6 M, respectively, whereas the IC50 of RNase alone was almost 10-4M. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. The conjugate showed no detectable cytotoxicity against EGF receptor-deficient small cell lung cancer cells (H69). Addition to excess EGF in the medium protected A431 cells from the EGF-RNase conjugate cytotoxicity. The cytotoxicity of the EGF-RNase conjugate was positively correlated with the EGF receptor numbers of each cell line. The chimeric toxin composed of only human proteins might be a more useful anti-cancer agent with less immunogenicity than the conventional chimeric toxins.
Original language | English |
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Pages (from-to) | 1901-1908 |
Number of pages | 8 |
Journal | Life Sciences |
Volume | 58 |
Issue number | 21 |
DOIs | |
Publication status | Published - Apr 19 1996 |
Keywords
- conjugate
- epidermal growth factor
- ribonuclease
- squamous carcinoma
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)