» Articles » PMID: 25486469

Sirtuin Deacetylases: a New Target for Melanoma Management

Overview
Journal Cell Cycle
Specialty Cell Biology
Date 2014 Dec 9
PMID 25486469
Citations 21
Authors
Affiliations
Soon will be listed here.
Abstract

Melanoma continues to cause more deaths than any other skin cancer, necessitating the development of new avenues of treatment. One promising new opportunity comes in the form of mechanism-based therapeutic targets. We recently reported the overexpression and delocalization of the class III histone deacetylase SIRT1 in melanoma, and demonstrated that its small molecule inhibition via Tenovin-1 decreased cell growth and viability of melanoma cells, possibly by a p53 mediated induction of p21. Here, we support our data using additional SIRT inhibitors, viz. Sirtinol and Ex-527, which suggests possible benefits of concomitantly inhibiting more than one Sirtuin for an effective cancer management strategy. This "Extra View" paper also includes a discussion of our results in the context of similar recent and concurrent studies. Furthermore, we expand upon our findings in an analysis of new research that may link the cellular localization and growth effects of SIRT1 with the PI3K signaling pathway.

Citing Articles

Selisistat, a SIRT1 inhibitor, enhances paclitaxel activity in luminal and triple-negative breast cancer: in silico, in vitro, and in vivo studies.

Wawruszak A, Luszczki J, Bartuzi D, Kalafut J, Okon E, Czerwonka A J Enzyme Inhib Med Chem. 2025; 40(1):2458554.

PMID: 39935420 PMC: 11823383. DOI: 10.1080/14756366.2025.2458554.


Melanoma Metabolism: Molecular Mechanisms and Therapeutic Implications in Cutaneous Oncology.

J Tan I, Parikh A, Cohen B Cancer Med. 2024; 13(21):e70386.

PMID: 39494561 PMC: 11532834. DOI: 10.1002/cam4.70386.


Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling.

Walker C, Batan D, Bishop C, Ramirez D, Aguado B, Schroeder M Bioeng Transl Med. 2022; 7(3):e10394.

PMID: 36176599 PMC: 9472021. DOI: 10.1002/btm2.10394.


Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways.

Kundu A, Gali S, Sharma S, Park J, Kyung S, Kacew S Antioxidants (Basel). 2022; 11(9).

PMID: 36139886 PMC: 9495519. DOI: 10.3390/antiox11091812.


Emerging Roles of Post-Translational Modifications in Skin Diseases: Current Knowledge, Challenges and Future Perspectives.

Yang L, Yan Y J Inflamm Res. 2022; 15:965-975.

PMID: 35177923 PMC: 8846607. DOI: 10.2147/JIR.S339296.


References
1.
Allison S, Milner J . SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways. Cell Cycle. 2007; 6(21):2669-77. DOI: 10.4161/cc.6.21.4866. View

2.
Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y . Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007; 282(9):6823-32. DOI: 10.1074/jbc.M609554200. View

3.
Bouras T, Fu M, Sauve A, Wang F, Quong A, Perkins N . SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem. 2005; 280(11):10264-76. DOI: 10.1074/jbc.M408748200. View

4.
Bhatia S, Tykodi S, Thompson J . Treatment of metastatic melanoma: an overview. Oncology (Williston Park). 2009; 23(6):488-96. PMC: 2737459. View

5.
Inoue T, Hiratsuka M, Osaki M, Oshimura M . The molecular biology of mammalian SIRT proteins: SIRT2 in cell cycle regulation. Cell Cycle. 2007; 6(9):1011-8. DOI: 10.4161/cc.6.9.4219. View