Glucose deprivation, a feature of poorly vascularized solid tumors, activates the unfolded protein response (UPR) which is a stress-signaling pathway in tumor cells that is associated with the molecular chaperone, glucose-regulated protein 78 (GRP78). Induction of GRP78 protects cells against programmed cell death. Methanolic extract of Carthamus tinctorius(CTE) induced selective cytotoxicity in glucose-deprived HT-29 human colon carcinoma cells; this effect was not seen under normal growth conditions. CTE also suppressed the accumulation of the GRP78 protein and was highly toxic in HT-29 cells, with IC50 values for colony formation of < 50 mg/ml under 2-deoxyglucose (2DG) supplemented and glucose-deprived conditions. Interestingly, apoptotic activity of CTE was also detected by Hoechst staining and flow cytometric analysis. Therefore, these results suggest that CTE prevent the up-regulation of GRP78 and exhibit selective cytotoxicity in glucose-deprived HT-29 cells.
Key words: Glucose deprivation, unfolded protein response, (glucose-regulated protein 78) GRP78, Carthamus tinctorius, HT-29 cells.
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