Effect of SIRT1 activators and inhibitors on CD44+/CD133+‑enriched non‑small cell lung cancer cells

Eroglu,Zuhal; Erdem,Ceren; Oktem,Gulperi; Bozok Cetintas,Vildan; Duzgun,Zekeriya

doi:10.3892/mmr.2020.11113

Effect of SIRT1 activators and inhibitors on CD44+/CD133+‑enriched non‑small cell lung cancer cells

Authors:
- Zuhal Eroglu
- Ceren Erdem
- Gulperi Oktem
- Vildan Bozok Cetintas
- Zekeriya Duzgun
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Affiliations: Department of Medical Biology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey, Department of Histology and Embryology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey, Department of Medical Biology, Faculty of Medicine, Giresun University, Debboy, Giresun 28100, Turkey
Published online on: May 4, 2020 https://doi.org/10.3892/mmr.2020.11113
Pages: 575-581

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Abstract

Lung cancer is one of the most commonly diagnosed cancers and it is associated with high rates of morbidity and mortality. Metastasis and relapse of the tumor depend on the survival and proliferation of lung cancer stem cells (LCSCs). The ability to identify CSCs may prevent recurrence and lead to more effective treatments. Sirtuins are a group of deacetylases that include seven variants (SIRT1‑7), with sirtuin 1 (SIRT1) being the most intensively investigated. Evidence suggests that SIRT1 is both a tumor‑suppressor gene and an oncogene. SIRT1 can deacetylate the tumor‑suppressor protein p53 to decrease its activity. SIRT1 activators increase the deacetylation of p53, whereas SIRT1 inhibitors can stimulate p53 by inhibiting deacetylation. In the present study, CD44+ and CD133+‑enriched A549 (non‑small cell lung cancer) cells collected using the CD44 and CD133 CSC surface markers by fluorescence‑activated cell sorting method were treated with SIRT1 inhibitors (tenovin‑6 and sirtinol) and SIRT1 activators (resveratrol and SRT1720), and their effects on apoptosis, as well as the mRNA and protein expression of SIRT1 and p53 were investigated. Of these agents, it was found that resveratrol increased p53 expression by 4.1‑fold, decreased SIRT1 expression by 0.2‑fold, and it was the most potent inducer of apoptosis.

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