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Hsp70 inhibition potentiates radicicol-induced cell death in anaplastic thyroid carcinoma cells
Si Hyoung Kim1, Jun Goo Kang1, Chul Sik Kim1
1Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
Background/Aim:
The aim of the present study was to evaluate the effect of radicicol, an inhibitor of heat shock protein (hsp) 90, alone or in combination with hsp70 inhibition on survival of anaplastic thyroid carcinoma (ATC) cells.
Materials And Methods:
Antitumor activity of radicicol-alone or in combination with the hsp70 inhibitor VER155008 was investigated in 8505C and CAL62 cells.
Results:
Radicicol decreased cell viability and Akt protein levels, and increased the percentage of dead cells and hsp70 protein levels. In PIK3CA plasmid-transfected cells, compared to cells treated with radicicol-alone, cell viability increased and cellular death decreased. In cells treated with both radicicol and VER155008, compared to cells treated with radicicol-alone, cell viability further decreased and the percentage of dead cells further increased, with a parallel decrease of the protein levels of heat shock cognate 70, Akt and survivin.
Conclusion:
Our results suggest that radicicol induces cell death mediated through PI3K/Akt signaling with modulation of hsp90 client proteins and hsp70 inhibition enhances radicicol-induced cell death with suppression of survivin in ATC cells.
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