Dendrosomal Nanocurcumin Induces Changes in the Expression Levels of Heat Shock Proteins in the AGS Cell Line: Cellular Tolerance or Smart Apoptosis Induction

Objectives:The expression levels of heat shock proteins (HSPs) are elevated in many cancers, and this overexpression is often associated with both a poor survival and a therapeutic outcome. Curcumin is an anti-cancer agent that also induces a heat shock response. HSPs confer resistance to curcumin-induced apoptosis in cancerous cells. The aim of the current study was to analyze variations in the expression levels of hsp gene in response to polymeric-nanocurcumin (DNC) to determine whether these alterations have inhibitory effects on apoptosis or promote it. Methods:The IC50 of DNC on AGS cell line was determined by the MTT assay. Following DNC treatment, the expression levels of hsp mRNAs were quantified by qPCR. Using siRNA, the Hsp27 gene was knocked down, and the DNC-induced apoptosis was determined by Annexin V test. Results: Three variants of Hsp27 and two members of Hsp40 and Hsp90 families were significantly up-regulated while one member of Hsp40 and Hsp70 families were down-regulated. As a result of Hsp27 knock down, the DNC-induced apoptosis was increased about 26% (26.19 vs 52.61). Conclusion:The overall effect of DNC on Hsp genes was induction, which suggests that DNC could cause stress in AGS cells. On the other hand, reduced levels of Hsp70-2 and DnaJC3 expression could be indicative of their involvement in DNC-induced apoptosis. In addition, as Hsp27 knock down led to an increase in apoptosis, it appears that Hsp27 confers resistance against DNC-induced apoptosis. Therefore, knock down of Hsp27gene could be considered as a supplementary treatment beside DNC in cancer therapy.