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

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Title
Selective cytotoxic activity of valinomycin against HT-29 Human colon carcinoma cells via down-regulation of GRP78
Author(s)
In Ja Ryoo; H R Park; Soo-Jin Choo; J H Hwang; Y M Park; K H Bae; K Shin-Ya; Ick Dong Yoo
Bibliographic Citation
Biological & Pharmaceutical Bulletin, vol. 29, no. 4, pp. 817-820
Publication Year
2006
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.
Keyword
endoplasmic reticulum stressGRP78HT-29unfolded protein responsevalinomycin
ISSN
0918-6158
Publisher
Pharmaceutical Soc Japan
DOI
http://dx.doi.org/10.1248/bpb.29.817
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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