title: AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells.
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.
authors.affiliation: 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.
authors.forename: Min Gyeong
authors.initials: MG
authors.lastname: Cheon
authors.affiliation: 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.
authors.forename: Wootae
authors.initials: W
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Minji
authors.initials: M
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Ja-Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013449:Sulfonamides / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D013449:Sulfonamides; D014157:Transcription Factors; C474199:SIRT2 protein, human; D056565:Sirtuin 2
keywords: AK-1; Cell cycle; G1 arrest; SIRT2; Snail