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Title 

Selective cytotoxic activity of valinomycin against HT-29 Human colon carcinoma cells via down-regulation of GRP78

Authors 

In Ja RyooH R ParkSoo-Jin ChooJ H HwangY M ParkK H BaeK Shin-YaIck Dong Yoo

Publisher 

Pharmaceutical Society of Japan

Issue Date 

2006

Citation 

Biological & Pharmaceutical Bulletin, vol. 29, no. 4, pp. 817-820

Keywords 

endoplasmic reticulum stressGRP78HT-29unfolded protein responsevalinomycincarcinoma cellcell deathcolon carcinomacytotoxicitydown regulation

Abstract 

Glucose deprivation is a fundamental feature of poorly vascularized solid tumors and leads to activation of the molecular chaperone GRP78, which is associated with the unfolded protein response (UPR), a stress-signaling pathway, in tumor cells. We recently isolated an active compound, M126, that inhibits transcription from a GRP78 promoter reporter construct. M126 was identified as valinomycin by various spectroscopic methods. We found that valinomycin prevents UPR-induced protein expression, such as GRP78 and GRP94. The GRPs-inhibitory action of valinomycin severe hypoglycemic and results in selective cell death of the stressed cancer cells. Our findings demonstrate that GRP78 may be an excellent target for the use of cancer chemotherapy in the treatment of solid tumors.

ISSN 

0918-6158

Link 

http://dx.doi.org/10.1248/bpb.29.817

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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