Hsp70 inhibition potentiates radicicol-induced cell death in anaplastic thyroid carcinoma cells.

Abstract

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.

• Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 9 Pg. 4829-37 (Sep 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25202064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• HSP70 Heat-Shock Proteins
• Macrolides
• Purine Nucleosides
• VER 155008
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• monorden

Topics

• Cell Death (drug effects)
• Cell Line, Tumor
• HSP70 Heat-Shock Proteins (antagonists & inhibitors, metabolism)
• Humans
• Macrolides (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Purine Nucleosides (pharmacology)
• Signal Transduction (drug effects)
• Thyroid Carcinoma, Anaplastic
• Thyroid Neoplasms (metabolism)