Epidermal growth factor receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human EGF and RNase 1

Hiromitsu Jinno, Masakazu Ueda, Soji Ozawa, Tadashi Ikeda, Kohji Enomoto, Kyriakos Psarras, Masaki Kitajima, Hidenori Yamada, Masaharu Seno

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish
Pages (from-to)1901-1908
Number of pages8
JournalLife Sciences
Volume58
Issue number21
DOIs
Publication statusPublished - 1996 Apr 19

Keywords

  • conjugate
  • epidermal growth factor
  • ribonuclease
  • squamous carcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Jinno, H., Ueda, M., Ozawa, S., Ikeda, T., Enomoto, K., Psarras, K., Kitajima, M., Yamada, H., & Seno, M. (1996). Epidermal growth factor receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human EGF and RNase 1. Life Sciences, 58(21), 1901-1908. https://doi.org/10.1016/0024-3205(96)00174-9