Potential antitumor therapeutic application of Grimontia hollisae thermostable direct hemolysin mutants

Sheng Cih Huang, Yu Kuo Wang, Wan Ting Huang, Tsam Ming Kuo, Bak Sau Yip, Tien Hsiung Thomas Li, Tung-Kung Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We report on the preparation of a new type of immunotoxin by conjugation of an epidermal growth factor receptor (EGFR)-binding peptide and an R46E mutation of thermostable direct hemolysin from Grimontia hollisae, (Gh-TDHR46E/EB). The hybrid immunotoxin was purified to homogeneity and showed a single band with slight slower mobility than that of Gh-TDHR46E. Cytotoxicity assay of Gh-TDHR46E/EB on EGFR highly, moderately, low, and non-expressed cells, A431, MDA-MB-231, HeLa, and HEK293 cells, respectively, showed apparent cytotoxicity on A431 and MDA-MB-231 cells but not on HeLa or HEK293 cells. In contrast, no cytotoxicity was observed for these cells treated with either Gh-TDHR46E or EB alone, indicating enhanced cytotoxic efficacy of Gh-TDHR46E by the EGFR binding moiety. Further antitumor activity assay of Gh-TDHR46E/EB in a xenograft model of athymic nude mice showed obvious shrinkage of tumor size and degeneration, necrosis, and lesions of tumor tissues compared to the normal tissues. Therefore, the combination of Gh-TDHR46E with target affinity agents opens new possibilities for pharmacological treatment of cancers and potentiates the anticancer drug's effect.

Original languageEnglish
Pages (from-to)447-454
Number of pages8
JournalCancer Science
Volume106
Issue number4
DOIs
StatePublished - 1 Apr 2015

Keywords

  • Grimontia hollisae
  • Anticancer
  • Epidermal growth factor receptor
  • Immunotoxin
  • Thermostable direct hemolysin

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