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

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.

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

“…SIRT1 has been reported to regulate neovascularization by reducing the transcriptional activity of P53 by deacetylation of its lysine residues ( 85 , 86 ). A study investigating the effects of SIRT1 activators and inhibitors on CD44+/CD133+-enriched NSCLC cells reported that SIRT1 can deacetylate the tumor suppressor protein P53, thereby decreasing its activity ( 87 ). Meanwhile, the modulation of SIRT1 expression by resveratrol promoted the collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells ( 88 ).…”

System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets

“…Thus, targeting at SIRT1 may be a good way for regulating the occurrence and development of LC. 38 VHL expression may be an important biological indicator of the occurrence, development, clinical biological behavior, and prognosis of LC. 39 Studies have found that LEF1 overexpression leads to enhanced LC cell proliferation and invasion.…”