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Assessment of SIRT2 Inhibitors in Mouse Models of Cancer

  • Yashira L. Negrón Abril
  • Irma Fernández
  • Robert S. WeissEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1983)

Abstract

New therapeutics directed against established and novel molecular targets are urgently needed to intervene against cancer. Recently, it was reported that several members of the sirtuin family (SIRT1–7), the mammalian orthologs of the silent information regulator 2 (Sir2) protein in Saccharomyces cerevisiae, play important roles in carcinogenesis. Although SIRT2 has been attributed both tumor-promoting and tumor-suppressing activities in different contexts, selective SIRT2 inhibition with a small molecule mechanism-based inhibitor known as Thiomyristoyl lysine (TM) repressed the growth of breast cancer cell lines. In light of the anticancer effect of SIRT2 inhibition in cell culture, it was critical to assess the efficacy of TM as a potential anticancer therapy in vivo. This was accomplished by testing the SIRT2 inhibitor in genetically engineered and xenotransplantation mouse models of breast cancer, using the procedures detailed in this chapter.

Keywords

Sirtuins SIRT2 Genetically engineered mouse model Xenograft Breast cancer Small molecule inhibitor 

Notes

Acknowledgments

This work was supported in part by an intercampus seed grant from Cornell University and NIH R01 grant CA163255. Y.L.N.A. and I.F. were supported by NIH grants T32 GM008500 and T32 GM007273, respectively. The authors thank Dr. Elizabeth Moore for comments on the manuscript, and Dr. Hening Lin and members of his laboratory for helpful discussions and providing TM compound.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yashira L. Negrón Abril
    • 1
  • Irma Fernández
    • 1
  • Robert S. Weiss
    • 1
    Email author
  1. 1.Department of Biomedical SciencesCornell UniversityIthacaUSA

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