Optimum modification for the highest cytotoxicity of cationized ribonuclease

Junichiro Futami, Emiko Nukui, Takashi Maeda, Megumi Kosaka, Hiroko Tada, Masaharu Seno, Hidenori Yamada

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Cationization of a protein is considered to be a powerful strategy for internalizing a functional protein into cells. Cationized proteins appear to adsorb to the cell surface by electrostatic interactions, then enter the cell in a receptor- and transporter-independent fashion. Thus, in principle, all cell types appear to take up cationized proteins. Since ribonucleases (RNases) have a latent cytotoxic potential, cationized RNases could be useful cancer chemotherapeutics. In this study, we investigated the effect of the degree of cationization on the cytotoxicity of RNase A by modifying carboxyl groups with ethylenediamine. We found that there is an optimum degree of modification for cytotoxicity, in which 5 to 7 out of 11 carboxyl groups in RNase A are modified, toward MCF-7 and 3T3-SV-40 cells. More interestingly, the cytotoxicity of cationized RNase As correlates well with the value of [RNase activity] x [estimated concentration of RNase free from RNase inhibitor], mimicking the practical enzymatic activity of cationized RNase As in cytosol. The results indicate that cationization of a protein to an optimum level is important for maintaining protein function in the cytosol. Sophisticated protein cationization techniques will help to advance protein transduction technology.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalJournal of biochemistry
Issue number2
Publication statusPublished - Aug 2002


  • Cationization
  • Cytotoxicity
  • Protein transduction
  • Ribonuclease

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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