Combining Sirtuin and HDAC Inhibitors to Treat Leukemia
Author Information
Author(s): Cea Michele, Soncini Debora, Fruscione Floriana, Raffaghello Lizzia, Garuti Anna, Emionite Laura, Moran Eva, Magnone Mirko, Zoppoli Gabriele, Reverberi Daniele, Caffa Irene, Salis Annalisa, Cagnetta Antonia, Bergamaschi Micaela, Casciaro Salvatore, Pierri Ivana, Damonte Gianluca, Ansaldi Filippo, Gobbi Marco, Pistoia Vito, Ballestrero Alberto, Patrone Franco, Bruzzone Santina, Nencioni Alessio
Primary Institution: Department of Internal Medicine, University of Genoa, Genoa, Italy
Hypothesis
The study investigates the antileukemic activity of sirtuin inhibitors and the NAD+-lowering drug FK866, both alone and in combination with traditional HDAC inhibitors.
Conclusion
Combining sirtuin inhibitors with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.
Supporting Evidence
- Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells.
- HDAC inhibitors induced upregulation of Bax, sensitizing leukemia cells to apoptosis.
- Healthy leukocytes and hematopoietic progenitors were not affected by the drug combinations.
Takeaway
This study shows that using two types of drugs together can help kill leukemia cells better than using them alone.
Methodology
Primary leukemia cells, leukemia cell lines, healthy leukocytes, and hematopoietic progenitors were treated with sirtuin inhibitors and HDAC inhibitors, and cell death was quantified using flow cytometry.
Limitations
The study does not explore the long-term effects of the drug combinations or their efficacy in vivo.
Participant Demographics
The study involved primary leukemia cells from patients and healthy leukocytes.
Digital Object Identifier (DOI)
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