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Ryoo IJ, Park HR, Choo SJ, Hwang JH, Park YM, Bae KH, Shin-Ya
K, Yoo ID.
Selective cytotoxic activity of valinomycin against HT-29
Human colon carcinoma cells via down-regulation of GRP78.
Biol Pharm Bull. 2006 Apr;29(4):817-20
Ryoo IJ, Park HR, Choo SJ, Hwang JH, Park YM, Bae KH, Shin-Ya
K, Yoo ID.
Laboratory of Antioxidant, Korea Research Institute of
Bioscience and Biotechnology, Daejeon, Korea.
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.
PMID: 16595926
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