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Article

Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities

  • Authors:
    • lijia Zhu
    • Ji Qi
    • Christine Ya-Chi Chiao
    • Qiang Zhang
    • John A. Porco Jr
    • douglas V. Faller
    • Yan Dai
  • View Affiliations / Copyright

    Affiliations: Cancer Research Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA, Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, Boston, MA 02215, USA
  • Pages: 2128-2136
    |
    Published online on: September 3, 2014
       https://doi.org/10.3892/ijo.2014.2639
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Abstract

SIRT1, a class III histone deacetylase, plays a critical role in regulating cancer cell growth, migration and invasion, which makes it a potential target for cancer therapeutics. In this study, we screened derivatives of several groups of natural products and identified a novel SIRT1 inhibitor JQ-101, a synthetic derivative of the polyprenylated acylphloroglucinol (PPAP) natural products, with an IC50 for SIRT1 of 30 µM in vitro, with 5-fold higher activity for SIRT1 vs. SIRT2. Exposure of tumor cells to JQ-101 significantly enhanced acetylation of p53 and histone H4K16 at known sites of SIRT1 deacetylation, validating SIRT1 as its cellular target. JQ-101 suppressed cancer cell growth and survival by targeting SIRT1, and also exhibited selective cytotoxicity towards a panel of human tumor cell lines, while producing no toxicity in two normal human cell types at comparable concentrations. JQ-101 induced both apoptosis and cell senescence, and suppressed cancer cell invasion in vitro. In summary, we have identified JQ-101 as a new SIRT1 inhibitor which may have potential application in cancer treatment through its ability to induce tumor cell apoptosis and senescence and suppress cancer cell invasion.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu l, Qi J, Chiao CY, Zhang Q, Porco Jr JA, Faller dV and Dai Y: Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities. Int J Oncol 45: 2128-2136, 2014.
APA
Zhu, l., Qi, J., Chiao, C.Y., Zhang, Q., Porco Jr, J.A., Faller, d.V., & Dai, Y. (2014). Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities. International Journal of Oncology, 45, 2128-2136. https://doi.org/10.3892/ijo.2014.2639
MLA
Zhu, l., Qi, J., Chiao, C. Y., Zhang, Q., Porco Jr, J. A., Faller, d. V., Dai, Y."Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities". International Journal of Oncology 45.5 (2014): 2128-2136.
Chicago
Zhu, l., Qi, J., Chiao, C. Y., Zhang, Q., Porco Jr, J. A., Faller, d. V., Dai, Y."Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities". International Journal of Oncology 45, no. 5 (2014): 2128-2136. https://doi.org/10.3892/ijo.2014.2639
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu l, Qi J, Chiao CY, Zhang Q, Porco Jr JA, Faller dV and Dai Y: Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities. Int J Oncol 45: 2128-2136, 2014.
APA
Zhu, l., Qi, J., Chiao, C.Y., Zhang, Q., Porco Jr, J.A., Faller, d.V., & Dai, Y. (2014). Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities. International Journal of Oncology, 45, 2128-2136. https://doi.org/10.3892/ijo.2014.2639
MLA
Zhu, l., Qi, J., Chiao, C. Y., Zhang, Q., Porco Jr, J. A., Faller, d. V., Dai, Y."Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities". International Journal of Oncology 45.5 (2014): 2128-2136.
Chicago
Zhu, l., Qi, J., Chiao, C. Y., Zhang, Q., Porco Jr, J. A., Faller, d. V., Dai, Y."Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities". International Journal of Oncology 45, no. 5 (2014): 2128-2136. https://doi.org/10.3892/ijo.2014.2639
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