Selective pharmacologic inhibition of c-Jun NH2-terminal kinase radiosensitizes thyroid anaplastic cancer cell lines via induction of terminal growth arrest

Dmitry Bulgin, Alexei Podtcheko, Shu Takakura, Norisato Mitsutake, Hiroyuki Namba, Vladimir Saenko, Akira Ohtsuru, Tatiana Rogounovitch, Iryna Palona, Shunichi Yamashita

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Context: The high radioresistance of anaplastic thyroid cancer (ATC) and cultured ATC cells stipulates for the means of increasing their radiosensitivity. It has been shown that c-Jun NH2-terminal kinase (JNK) activation is one of the manifestations of radiation response in ATC cells. Objective: Assessment of the effect of selective JNK inhibition on ATC cell radiosensitivity and clarification of the associated mechanisms. Results: The JNK inhibitor markedly suppressed ATC cell growth in a reversible cytostatic manner. The combination treatment with JNK inhibitor plus ionizing radiation induced a significant decrease in clonogenic survival of irradiated cells as compared with either singular treatment. The effect was not due to apoptosis of exposed cells but to a profound senescence-like terminal growth arrest occurring irrespectively of cells' p53 mutational status. Postradiational DNA damage repair was also significantly compromised in the presence of SP600125. Conclusions: JNK signaling is an essential component of ATC cell proliferation and survival after radiation therapy. Hence, pharmacological interference with JNK pathway in combination with radiotherapy may be a promising treatment of ATC.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalThyroid
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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