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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Cheon MG,Kim W,Choi M,Kim JEdoi
10.1016/j.canlet.2014.10.012subject
Has Abstractpub_date
2015-01-28 00:00:00pages
637-45issue
2 Pt Beissn
0304-3835issn
1872-7980pii
S0304-3835(14)00600-4journal_volume
356pub_type
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