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Assessment of SIRT2 Inhibitors in Mouse Models of Cancer

Yashira L Negrón Abril1, Irma Fernández1, Robert S Weiss2

  • 1Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.

Methods in Molecular Biology (Clifton, N.J.)
|May 16, 2019
PubMed

Insights

Selective SIRT2 inhibition using Thiomyristoyl lysine (TM) repressed breast cancer cell growth in vitro. This study evaluated TM

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sirtuin family members (SIRT1-7) are implicated in carcinogenesis.
  • SIRT2 exhibits context-dependent tumor-promoting and tumor-suppressing roles.
  • Selective SIRT2 inhibition with Thiomyristoyl lysine (TM) showed anticancer effects in breast cancer cell lines.

Purpose of the Study:

  • To evaluate the in vivo efficacy of Thiomyristoyl lysine (TM) as a breast cancer therapeutic.
  • To assess the anticancer potential of SIRT2 inhibition in preclinical models.

Main Methods:

  • Testing the SIRT2 inhibitor TM in genetically engineered mouse models of breast cancer.
  • Evaluating TM efficacy in xenotransplantation mouse models of breast cancer.

Main Results:

  • Selective SIRT2 inhibition with TM repressed breast cancer cell line growth in vitro.
  • In vivo efficacy of TM in mouse models of breast cancer was assessed (details in chapter).

Conclusions:

  • SIRT2 inhibition warrants further investigation as a potential breast cancer therapy.
  • TM demonstrates potential as an anticancer agent for breast cancer treatment.
Keywords:
Breast cancerGenetically engineered mouse modelSIRT2SirtuinsSmall molecule inhibitorXenograft

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