1. Academic Validation
  2. AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells

AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells

  • Cancer Lett. 2015 Jan 28;356(2 Pt B):637-45. doi: 10.1016/j.canlet.2014.10.012.
Min Gyeong Cheon 1 Wootae Kim 1 Minji Choi 1 Ja-Eun Kim 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea.
  • 2 Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: jekim@khu.ac.kr.
Abstract

SIRT2, a member of the Sirtuin family, is involved in the regulation of a variety of physiological functions. In addition, SIRT2 has been studied in the context of pathological conditions including neurodegenerative diseases, metabolic syndrome, and Cancer. The effect of SIRT2 on Cancer cell growth depends on Cancer tissue type. To investigate the role of SIRT2 in colon Cancer, we treated HCT116 human colon Cancer cells with the SIRT2-specific inhibitor AK-1, a cell-permeable benzylsulfonamide. AK-1 treatment induced proteasomal degradation of the Snail transcription factor through inactivation of the NF-κB/CSN2 pathway. Reduction in the level of Snail resulted in upregulation of p21, a cyclin-dependent kinase inhibitor, leading to G1 arrest, slow proliferation, and slow wound-healing activity. The regulation of Snail-p21 axis by AK-1 also occurs in HT-29 colon Cancer cells. Therefore, inhibition of SIRT2 using AK-1 would be a beneficial intervention in the treatment of colon Cancer.

Keywords

AK-1; Cell cycle; G1 arrest; SIRT2; Snail.

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