Induction of apoptosis in human follicular thyroid cancer cells by the histone deacetylase inhibitors TSA and FK228

Abstract

Abstract Introduction: The histone deacetylase (HDAC) inhibitors are a heterogeneous group of compounds that alter the chromatin structure of neoplastic cells, causing cell-cycle arrest, redifferentiation, and apoptosis. TSA and FK228 are structurally different HDAC inhibitors that have been used for the treatment of several cancers in laboratory and clinical trials. The effects of TSA and FK228 on apoptosis have not been fully characterized or quantitated. We studied the effects of TSA and FK228 on apoptosis in a human follicular thyroid cancer cell line (FTC-236). Methods: We treated FTC-236 cells with TSA (25–100 ng/ml) and FK228 (0.1–1 ng/ml). Apoptosis was measured at 24 and 48 hours after treatment using annexin V-FITC labeling and flow cytometry. RNA was extracted at 24 and 48 hours and real-time PCR was performed to measure gene expression levels of bcl-2 and bcl-xl, two pro-survival proteins that function in the regulation of apoptosis. Results: At 48 hours after treatment, 6.4% of TSA-treated FTC-236 cells underwent apoptosis; 25.7% of FK228-treated cells underwent apoptosis in the same time period (p Conclusions: TSA and FK228 have differing effects on apoptosis and pro-survival gene expression in FTC-236 cells. A better understanding of the effects of HDAC inhibitors on apoptosis will allow clinicians to design treatment regimens based on the genetic profiles and tumor behavior of the targeted malignancies.