Regression of solid tumors by induction of MazF, a bacterial mRNA endoribonuclease

Tsutomu Shimazu, Oleg Mirochnitchenko, Sangita Phadtare, Masayori Inouye

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

MazF from Escherichia coli is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. Its induction in mammalian cells has been shown to cause programmed cell death. Here we explored if a bacterial MazF-MazE toxin-antitoxin system can be used for gene therapy. For this, we first constructed a tetracycline-inducible MazF expression system in human embryonic kidney cells (T-Rex 293- mazF ). Solid tumors were formed by injecting T-Rex 293- mazF cells into nude mice. All 8 mice injected with the cells developed solid tumors, which regressed upon induction of MazF. In 4 mice, tumors completely regressed, while in the remaining 4 mice, tumors reappeared after apparent significant regression, which was found to be due to the lack of presence of functional MazF. Notably, the MazF-mediated regression of the tumors was counteracted by the expression of its cognate antitoxin MazE. These results indicate that a bacterial MazF-MazE toxin-antitoxin system may have potential to be used as a therapeutic tool.

Original languageEnglish (US)
Pages (from-to)228-233
Number of pages6
JournalJournal of molecular microbiology and biotechnology
Volume24
Issue number4
DOIs
StatePublished - Nov 7 2014

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Microbiology
  • Applied Microbiology and Biotechnology
  • Molecular Biology

Keywords

  • MazF
  • TA toxins
  • Tumor regression

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