Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor

Mitsuyasu Nakamura, Hidetsugu Saito, Hirotoshi Ebinuma, Kanji Wakabayashi, Yoshimasa Saito, Tamako Takagi, Nobuhiro Nakamoto, Hiromasa Ishii

研究成果: Article査読

35 被引用数 (Scopus)

抄録

The presence of telomerase has been demonstrated recently in many different malignancies. Several reports documented that in human hepatocellular carcinoma, the level of telomerase activity parallels its differentiation stage. In the present study, the effect of the differentiation-inducing agent sodium butyrate on telomerase activity in four human liver cancer cell lines was investigated using the telomeric repeat amplification protocol. We assayed telomerase activity before and after butyrate treatment and in cell cycle synchronized non-dividing quiescent cells. In addition, telomerase reverse transcriptase levels were measured at the mrna level. All four cell lines possessed high but not identical levels of telomerase activity. Telomerase activity was significantly reduced by treatment with sodium butyrate as well as trichostatin A in a dose- and time-dependent fashion, paralleling the reduction of cell proliferation. Although methotrexate, hydroxyurea, and colchicine synchronized the cell cycle at G1, S, and G2/m, respectively, and thereby also caused proliferating cells to cease dividing and become quiescent, in this case telomerase activity remained essentially unaltered compared to the control cultures. Moreover, levels of mrna encoding telomerase reverse transcriptase were not always significantly altered by either sodium butyrate treatment or cell cycle synchronization. These results suggest that sodium butyrate, as a histone deacetylase inhibitor, effectively reduces telomerase activity without affecting transcription levels of the reverse transcriptase component.

本文言語English
ページ(範囲)392-401
ページ数10
ジャーナルJournal of Cellular Physiology
187
3
DOI
出版ステータスPublished - 2001 5月 8

ASJC Scopus subject areas

  • 生理学
  • 臨床生化学
  • 細胞生物学

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