title: Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1.
abstract: SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD(+)-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC.
authors: Department of Otolaryngology, Gongli Hospital, Second Military Medical University, Pudong New Area, Miaopu Road 219, Shanghai, 200135, China.
authors: An
authors: A
authors: Hu
authors: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Huaihai Xi Road 241, Xuhui District, Shanghai 200030, China.
authors: Jing-Juan
authors: JJ
authors: Huang
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China.
authors: Rui-Lin
authors: RL
authors: Li
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China.
authors: Zhao-Yang
authors: ZY
authors: Lu
authors: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China.
authors: Jun-Li
authors: JL
authors: Duan
authors: Department of Otolaryngology, Gongli Hospital, Second Military Medical University, Pudong New Area, Miaopu Road 219, Shanghai, 200135, China.
authors: Wei-Hua
authors: WH
authors: Xu
authors: Department of Otolaryngology, Gongli Hospital, Second Military Medical University, Pudong New Area, Miaopu Road 219, Shanghai, 200135, China.
authors: Xiao-Ping
authors: XP
authors: Chen
authors: Department of Otolaryngology, Gongli Hospital, Second Military Medical University, Pudong New Area, Miaopu Road 219, Shanghai, 200135, China.|Department of Otolaryngology-Head &Neck Surgery, ChangZheng Hospital, Second Military Medical University, Fengyang Road 415, Huangpu District, Shanghai, 200003, China.
authors: Jing-Ping
authors: JP
authors: Fan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D053181:Caspase 8; D053453:Caspase 9; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D003474:Curcumin