Title: Potential antitumor therapeutic application of Grimontia hollisae thermostable direct hemolysin mutants
Authors: Huang, Sheng-Cih
Wang, Yu-Kuo
Huang, Wan-Ting
Kuo, Tsam-Ming
Yip, Bak-Sau
Li, Tien-Hsiung Thomas
Wu, Tung-Kung
Department of Biological Science and Technology
Keywords: Anticancer;epidermal growth factor receptor;Grimontia hollisae;immunotoxin;thermostable direct hemolysin
Issue Date: 1-Apr-2015
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.
URI: http://dx.doi.org/10.1111/cas.12623
ISSN: 1347-9032
DOI: 10.1111/cas.12623
Volume: 106
Begin Page: 447
End Page: 454
Appears in Collections:Articles