J Korean Surg Soc.  2008 Sep;75(3):162-170.

The Antiproliferative and Redifferentiative Effects of Na-4-Phenylbutyrate in Human Thyroid Cancer Cell Lines

• Choi YJ
• Park JW
• Jang LC
• Choi JW
• Clark OH

Abstract

PURPOSE: Sodium-4-phenylbutyrate (Na-4-PB) is an analogue of phenylacetate, which is a well-known redifferentiating agent. In vitro and in vivo studies on this agent have been done and the clinical relevance of Na-4-PB has been studied in other malignancies, but not in thyroid cancer. We investigated the effect of Na-4-PB on cell proliferation and differentiation in thyroid cancer cell lines.
METHODS
We used 5 thyroid cancer cell lines: TPC-1, FTC-133, FTC-236, FTC-238 and XTC-1. MTT assay and flowcytometry were used to measure the agent's antiproliferative effects and the cell cycle change. We evaluated the PPARgamma expression via western blotting and the mRNA expressions of NIS, Tg and CD 97 were determined by performing RT-PCR. Troglitazone, a potent PPARgamma agonist, was used in combined treatment with Na-4-PB.
RESULTS
Na-4-PB inhibited cell proliferation in a dose and time dependent manner in all 5 thyroid cancer cell lines. By performing flowcytometry in the FTC-133 and TPC-1 cell lines, we identified that the antiproliferative effect of Na-4-PB was associated with an increased apoptotic cell population. Treatment with Na-4-PB upregulated the PPARgamma expression, but the combined treatment of Na-4-PB with troglitazone did not seem to be synergistic for the antiproliferative effect. Treatment with Na-4-PB downregulated the CD97 mRNA expression and it upregulated the NIS and Tg mRNA expressions in both the FTC-133 and TPC-1 cell lines.
CONCLUSION
Na-4-PB inhibited thyroid cancer cell proliferation by inducing apoptosis in a dose dependent manner. Treatment with Na-4-PB increased the expression of PPARgamma and it upregulated such differentiation markers as NIS and Tg, and it downregulated CD97, a dedifferentiation marker. Na-4-PB should be further evaluated as a new potential therapeutic agent for patients with thyroid cancer.

Keyword

Na-4-PB; Histone deacetylase inhibitor; Thyroid cancer cell lines; CD 97; NIS

MeSH Terms

Antigens, Differentiation
Apoptosis
Blotting, Western
Cell Cycle
Cell Line
Cell Proliferation
Chromans
Histone Deacetylase Inhibitors
Humans
Phenylacetates
PPAR gamma
RNA, Messenger
Thiazolidinediones
Thyroid Gland
Thyroid Neoplasms
Antigens, Differentiation
Chromans
Histone Deacetylase Inhibitors
PPAR gamma
Phenylacetates
RNA, Messenger
Thiazolidinediones