17-Allylamino-17-demethoxygeldanamycin and Herbimycin A Induce Cell Death by Modulating β-Catenin and PI3K/AKT Signaling in FRO Anaplastic Thyroid Carcinoma Cells.

Abstract

AIM:

The aim of the present study was to evaluate the effect of heat-shock protein 90 (HSP90) inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and herbimycin A (HMA) on survival of anaplastic thyroid carcinoma (ATC) cells.

MATERIALS AND METHODS:

Antitumor activities of 17-AAG and HMA were investigated in FRO ATC cells.

RESULTS:

In FRO ATC cells, 17-AAG and HMA caused cell death with concomitant changes in the expression of HSP90 client proteins, increased β-catenin protein levels, and inhibited PI3K/AKT signaling. The inactivation of β-catenin by β-catenin siRNA transfection and the activation of PI3K/AKT signaling by p110α plasmid transfection abrogated cell death caused by 17-AAG and HMA.

CONCLUSION:

17-AAG and HMA have cytotoxic activities accompanied by regulation of HSP90 client proteins, and cytotoxicity is associated with overexpression of β-catenin and suppression of PI3K/AKT signaling in FRO 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. 35 Issue 10 Pg. 5453-60 (Oct 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26408708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Benzoquinones
• HSP90 Heat-Shock Proteins
• Lactams, Macrocyclic
• beta Catenin
• Rifabutin
• tanespimycin
• herbimycin
• Proto-Oncogene Proteins c-akt

Topics

• Antibiotics, Antineoplastic (pharmacology)
• Benzoquinones (pharmacology)
• Cell Death
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (drug effects)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• Lactams, Macrocyclic (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rifabutin (analogs & derivatives, pharmacology)
• Signal Transduction (drug effects)
• Thyroid Carcinoma, Anaplastic (drug therapy, metabolism)
• Thyroid Neoplasms (drug therapy, metabolism)
• beta Catenin (metabolism)