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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 81 - 88 (8page)
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Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identifi ed and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at $G_2$/M phase. At the same time, IN-2001 treatment time-dependently increased sub-$G_1$ population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased $p21^{WAF1}$ and $p27^{KIP1}$ expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.
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참고문헌 (37)
참고문헌 신청
Archer, S. Y. / 1998 / p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells / Proc. Natl. Acad. Sci. USA 95:6791~6796
Banwell, C. M. / 2003 / Antiproliferative signalling by 1,25(OH)2D3 in prostate and breast cancer is suppressed by a mechanism involving histone deacetylation / Recent Results Cancer Res 164:83~98
Bereshchenko, O. R. / 2002 / Acetylation inactivates the transcriptional repressor BCL6 / Nat. Genet 32:606~613
Biswas, S. / 2006 / Inhibition of transforming growth factor-beta signaling in human cancer: targeting a tumor suppressor network as a therapeutic strategy / Clin. Cancer Res 12:4142~4146
Blobel, G. A. / 2000 / CREB-binding protein and p300: molecular integrators of hematopoietic transcription / Blood 95:745~755
Banwell, C. M. / 2003 / Antiproliferative signalling by 1,25(OH)2D3 in prostate and breast cancer is suppressed by a mechanism involving histone deacetylation / Recent Results Cancer Res 164:83~98
Bereshchenko, O. R. / 2002 / Acetylation inactivates the transcriptional repressor BCL6 / Nat. Genet 32:606~613
Biswas, S. / 2006 / Inhibition of transforming growth factor-beta signaling in human cancer: targeting a tumor suppressor network as a therapeutic strategy / Clin. Cancer Res 12:4142~4146
Blobel, G. A. / 2000 / CREB-binding protein and p300: molecular integrators of hematopoietic transcription / Blood 95:745~755
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