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Inhibition of heat shock proteins (HSP) expression by quercetin and differential doxorubicin sensitization in neuroblastoma and Ewing’s sarcoma cell lines
Author(s) -
Zanini Cristina,
Giribaldi Giuliana,
Mandili Giorgia,
Carta Franco,
Crescenzio Nicoletta,
Bisaro Brigitte,
Doria Alessandra,
Foglia Luiselda,
Di Montezemolo Luca Cordero,
Timeus Fabio,
Turrini Franco
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04835.x
Subject(s) - doxorubicin , hsf1 , heat shock protein , gene silencing , neuroblastoma , sensitization , cell culture , biology , cancer research , cancer cell , quercetin , microbiology and biotechnology , apoptosis , hsp70 , chemistry , cancer , immunology , biochemistry , chemotherapy , gene , genetics , antioxidant
Neuroblastoma (NB) and Ewing’s sarcoma (ES) represent the most common extracranial solid tumors of childhood. Heat shock proteins (HSP) are elevated in cancer cells and their over‐expression was correlated to drug‐resistance. In this work we identified the HSP by a sensitive proteomic analysis of NB and ES cell lines, then, we studied the HSP response to doxorubicin. Some identified HSP were constitutively more expressed in NB than in ES cells. Doxorubicin‐stimulated HSP response only in NB cells. Quercetin was found to inhibit HSP expression depleting heat shock factor 1 (HSF1) cellular stores. Quercetin caused a higher anti‐proliferative effect in NB (IC 50 : 6.9 ± 5.8 μmol/L) than in ES cells (IC 50 : 85.5 ± 53.1 μmol/L). Moreover, quercetin caused a very pronounced doxorubicin sensitizing effect in NB cells (241 fold IC 50 decrease) and a moderate effect in ES cells. HSP involvement in NB cells sensitization was confirmed by the silencing of HSF1. Quercetin treatment and HSF1 silencing increased the pro‐apoptotic effect of doxorubicin. In conclusion, the higher HSP levels, observed in NB cells, did not confer increased resistance to doxorubicin; on the contrary, HSP inhibition by quercetin or gene silencing caused higher sensitization to doxorubicin. These results may have a potential application in the treatment of NB.