# Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1

**Authors:** An Hu, Jing-Juan Huang, Rui-Lin Li, Zhao-Yang Lu, Jun-Li Duan, Wei-Hua Xu, Xiao-Ping Chen, Jing-Ping Fan

PMC · DOI: 10.1038/srep13429 · Scientific Reports · 2015-08-24

## TL;DR

This study shows that curcumin, a compound from turmeric, can fight head and neck cancer by activating SIRT1 and triggering cell death.

## Contribution

The study reveals curcumin's anticancer mechanism via SIRT1 activation in head and neck squamous cell carcinoma.

## Key findings

- Curcumin inhibits cancer cell growth and induces apoptosis in FaDu and Cal27 cells.
- Curcumin reduces cancer migration and angiogenesis by activating apoptotic pathways.
- Curcumin activates the ATM/CHK2 pathway and inhibits nuclear factor-κB in cancer cells.

## 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.

## Linked entities

- **Genes:** SIRT1 (sirtuin 1) [NCBI Gene 23411], Casp9 (caspase 9) [NCBI Gene 12371], casp8 (caspase 8, apoptosis-related cysteine peptidase) [NCBI Gene 58022], ATM (ATM serine/threonine kinase) [NCBI Gene 472], CHEK2 (checkpoint kinase 2) [NCBI Gene 11200]
- **Chemicals:** curcumin (PubChem CID 969516)
- **Diseases:** head and neck squamous cell carcinoma (MONDO:0010150)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** PLAU (plasminogen activator, urokinase) [NCBI Gene 5328] {aka ATF, BDPLT5, QPD, UPA, URK, u-PA}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, Chek2 (checkpoint kinase 2) [NCBI Gene 50883] {aka CHK2, Cds1, HUCDS1, Rad53}, CHEK2 (checkpoint kinase 2) [NCBI Gene 11200] {aka CDS1, CHK2, HuCds1, LFS2, PP1425, RAD53}, FADD (Fas associated via death domain) [NCBI Gene 8772] {aka GIG3, IMD90, MORT1}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, H4C6 (H4 clustered histone 6) [NCBI Gene 8361] {aka H4, H4/c, H4FC, HIST1H4F}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, H1-0 (H1.0 linker histone) [NCBI Gene 3005] {aka H1.0, H10, H1F0, H1FV}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, SIRT2 (sirtuin 2) [NCBI Gene 22933] {aka SIR2, SIR2L, SIR2L2}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Casp8 (caspase 8) [NCBI Gene 12370] {aka CASP-8, FLICE, MACH, Mch5}, Mmp2 (matrix metallopeptidase 2) [NCBI Gene 17390] {aka Clg4a, GelA, MMP-2}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Casp9 (caspase 9) [NCBI Gene 12371] {aka APAF-3, CASP-9, Caspase-9, ICE-LAP6, Mch6}, CASP7 (caspase 7) [NCBI Gene 840] {aka CASP-7, CMH-1, ICE-LAP3, LICE2, MCH3}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, REL (REL proto-oncogene, NF-kB subunit) [NCBI Gene 5966] {aka C-Rel, HIVEN86A, IMD92}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}
- **Diseases:** Tumor (MESH:D009369), HNSCC (MESH:D000077195), squamous cell carcinoma (MESH:D002294), metastasis (MESH:D009362), pancreatic adenocarcinoma (MESH:D010190), carcinogenesis (MESH:D063646), toxicity (MESH:D064420),  (MESH:D006258)
- **Chemicals:** carboxymethylcellulose (MESH:D002266), crystal violet (MESH:D005840), polyphenol (MESH:D059808), KU-55933 (MESH:C495818), NAD(+) (MESH:D009243), glucose (MESH:D005947), O-acetyl-ADP-ribose (MESH:D038961), PEG400 (MESH:C000595213), Trichostatin A (MESH:C012589), water (MESH:D014867), Curcumin (MESH:D003474), TRIzol (MESH:C411644), Ca2+ (-), methanol (MESH:D000432), propidium iodide (MESH:D011419), hematoxylin (MESH:D006416), CO2 (MESH:D002245), streptomycin (MESH:D013307), MTT (MESH:C070243), transresveratrol (MESH:D000077185), nicotinamide (MESH:D009536), agarose (MESH:D012685), penicillin (MESH:D010406),  (MESH:D000970)
- **Species:** Homo sapiens (human, species) [taxon 9606], Curcuma longa (turmeric, species) [taxon 136217], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** 7F-H — Mus musculus (Mouse), Hybridoma (CVCL_B0HP), Cal27 — Homo sapiens (Human), Tongue adenosquamous carcinoma, Cancer cell line (CVCL_1107), FaDu — Homo sapiens (Human), Hypopharyngeal squamous cell carcinoma, Cancer cell line (CVCL_1218)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC4547100/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4547100/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC4547100/full.md

---
Source: https://tomesphere.com/paper/PMC4547100