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Open Access

Salermide down-regulates sirtuin proteins to induce human cancer cell apoptosis

BMC Pharmacology201111(Suppl 2):A49

https://doi.org/10.1186/1471-2210-11-S2-A49

Published: 5 September 2011

Background

The NAD+-dependent family of sirtuin proteins (SIRT1–7), is involved in cell apoptosis and senescence. Salermide is a potent inhibitor of SIRT1 and SIRT2 and can induce tumor-specific cell death in selected human cell lines. In this study we investigated salermide’s apoptotic effect in a wide range of other human cancer cell lines and its antiproliferative potential in combination with cisplatin.

Methods

Seven different cancer cell lines (SKOV-3, MKN45, MKN28, N87, FaDu, NuLi1, Jurkat) were treated with salermide (1 µM – 0.1 nM) for 24, 48, and 72 hours and assessed for cell viability. Three cell lines (SKOV-3, N87, Jurkat) were selected for combination therapy with salermide and cisplatin (30 µM). In order to characterize salermide’s proapoptotic pathway SIRT1, SIRT2, pAKt, p53, acetyl-p53 and Nampt (nicotinamide phosphoribosyltransferase) were determined in SKOV-3 and Jurkat cells by Western blotting.

Results

Salermide yielded greater dose-dependent apoptotic effects in Jurkat, SKOV-3 and N87 cells than in the other cell lines, with most potent effect after 48 h of incubation. The anti-proliferative activity was associated with a G0-G1 cell cycle arrest. SIRT1 and SIRT2 protein were down-regulated after 48 h and 72 h. This was accompanied by a down-regulation of pAKT, p53 and Nampt. Acetyl-p53 levels were not consistent across cell types. Cisplatin exerted synergistic effects with salermide in all cell lines and reduced cell viability up to 50%.

Conclusions

Salermide-induced apoptosis is cell line-dependent and more effective in slow-proliferating (SKOV-3) and hematologic (Jurkat) cancer cells. The synergism with cisplatin implies a potentiating effect of this sirtuin inhibitor as add-on in clinical cancer therapy.

Authors’ Affiliations

(1)
Department of Clinical Pharmacology, Medical University of Vienna

Copyright

© Leisser et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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