Resveratrol differentially regulates NAMPT and SIRT1 in hepatocarcinoma cells and primary human hepatocytes

Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Barnikol-Oettler, Anja; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

doi:10.1186/2049-3002-2-s1-p65

Cited by 3 publications

(5 citation statements)

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“…Cell culture medium was replaced with fresh medium after 24 h and collected after a further 24 h. eNAMPT levels were detected with a commercial kit (AdipoGen Life Sciences, Liestal, Switzerland) or semiquantitatively via Western blot analysis. eNAMPT enzymatic activity in concentrated supernatants of MCF-7 (pRS and SIRT6 sh2) cells was measured as described by Schuster et al (30).…”

Section: Assay Of Enampt Levels and Activitymentioning

confidence: 99%

SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells

et al. 2018

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Nicotinamide phosphoribosyltransferase (NAMPT) is the rate‐limiting enzyme in the NAD+ salvage pathway from nicotinamide. By controlling the biosynthesis of NAD+, NAMPT regulates the activity of NAD+‐converting enzymes, such as CD38, poly‐ADP‐ribose polymerases, and sirtuins (SIRTs). SIRT6 is involved in the regulation of a wide number of metabolic processes. In this study, we investigated the ability of SIRT6 to regulate intracellular NAMPT activity and NAD(P)(H) levels. BxPC‐3 cells and MCF‐7 cells were engineered to overexpress a catalytically active or a catalytically inactive SIRT6 form or were engineered to silence endogenous SIRT6 expression. In SIRT6‐overexpressing cells, NAD(H) levels were up‐regulated, as a consequence of NAMPT activation. By immunopurification and incubation with recombinant SIRT6, NAMPT was found to be a direct substrate of SIRT6 deacetylation, with a mechanism that upregulates NAMPT enzymatic activity. Extracellular NAMPT release was enhanced in SIRT6‐silenced cells. Also glucose‐6‐phosphate dehydrogenase activity and NADPH levels were increased in SIRT6‐overexpressing cells. Accordingly, increased SIRT6 levels reduced cancer cell susceptibility to H2O2‐induced oxidative stress and to doxorubicin. Our data demonstrate that SIRT6 affects intracellular NAMPT activity, boosts NAD(P)(H) levels, and protects against oxidative stress. The use of SIRT6 inhibitors, together with agents inducing oxidative stress, may represent a promising treatment strategy in cancer.—Sociali, G., Grozio, A., Caffa, I., Schuster, S., Becherini, P., Damonte, P., Sturla, L., Fresia, C., Passalacqua, M., Mazzola, F., Raffaelli, N., Garten, A., Kiess, W., Cea, M., Nencioni, A., Bruzzone, S. SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells. FASEB J. 33, 3704–3717 (2019). http://www.fasebj.org

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Section: Assay Of Enampt Levels and Activitymentioning

confidence: 99%

SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells

et al. 2018

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“…Sirt1 has been reported to deacetylate the lysine residue 382 of P53, a tumor‐suppressor protein, inducing its suppression as well as subsequent tumorigenesis. Therefore, Sirt1 suppression could lead to cancer cell death via activation and regulation of P53 (Schuster et al, ). Here, we further examined the relationship of NAMPT protein expression and the clinicopathological characteristics, demonstrating that NAMPT inhibition via the inhibitor FK866 or lentivirus‐mediated knockdown induced CRC cell growth and apoptosis via the Sirt1/P53 signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, NAMPT plays a very active role in catalyzing the rate-limiting step of nicotinamide condensation with 5-phosphoribosyl-1-pyrophosphate to produce nicotinamide mononucleotide (NMN) and subsequently NMNAT1, leading to NAD from NMN and ATP. The upregulation of NAMPT has been detected in multiple solid tumors, such as CRC, prostate cancer, and hepatocarcinoma (Lv et al, 2015;Schuster et al, 2014;Wang et al, 2011). Therefore, NAMPT is likely to be a potential therapeutic target for CRC by disturbing the metabolism of cancer cells via NAD reduction.…”

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confidence: 99%

Nicotinamide phosphoribosyl transferase regulates cell growth via the Sirt1/P53 signaling pathway and is a prognosis marker in colorectal cancer

Pan

Zhou

Zhu

et al. 2018

Journal Cellular Physiology

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Colorectal cancer (CRC) is the third most common malignancy, and the metabolic properties of CRC cells include enhanced aerobic glycolysis (the Warburg effect). Nicotinamide phosphoribosyl transferase (NAMPT) is one of the crucial enzymes that regulate the activity of nicotinamide adenine dinucleodinucleotide dependent enzymes. Targeting NAMPT is a potential method of CRC therapy. Nevertheless, the underlying clinical implications and regulatory mechanisms of NAMPT in CRC remain unclear. In this study, we showed that NAMPT protein expression was increased in subjects with rectal localization compared with those with colon localization, and NAMPT was a poor prognostic marker for the overall survival rate in patients with CRC. In addition, the NAMPT inhibitor FK866 or lentivirus-mediated silencing induced CRC cell growth inhibition. Mechanistically, NAMPT regulated Sirt1 and P53 expression and induced G0/G1 cell cycle arrest, along with the upregulation of downstream p21 and downregulation of cyclin D1, cyclin E1, and cyclin E2 expression. FK866 administration or knockdown of NAMPT induced CRC cell apoptosis via upregulation of caspase-3. In conclusion, NAMPT regulated Sirt1/P53 signaling during CRC cell growth and warrants further investigation for clinical administration in CRC.

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“…NO production was determined by measuring the level of nitrite in the culture supernatant of RAW 264.7 cells. The RAW264.7 cells were seeded at a density of 5×10 5…”

Section: Inhibition Of No Production In Lpsstimulated Raw 2647 Cellsmentioning

confidence: 99%

“…Since then, Res has been shown to exert a variety of pharmacological effects such as antioxidant, antidiabetes, anti-inflammatory and anti-cancer activities. RES is a natural compound currently under investigation due to its important biological anticancer properties, including effects on leukemia, skin, breast, lung gastric, colorectal, neuroblastoma, pancreatic and hepatoma cancers [3][4][5][6][7]. Polydatin or piceid (PD, Fig.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Nitric Oxide Scavenging and Nitric Oxide Synthases Expression of Resveratrol and Polydatin

Wang¹,

Lai²,

Wu³

et al. 2021

Proceedings of the 2021 10th International Conference on Applied Science, Engineering and Technology (ICASET 2021)

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Cellular damage induced by free-radicals like reactive oxygen species(ROS) has been implicated in several diseases. The ROS radicals like alkoxy radical(RO-) and peroxy radical (ROO-) are similar to those that are physiologically active and thus might initiate a cascade of intracellular toxic events leading to DNA damage and cell death. Hence naturally anti-oxidant play a vital role in combating these conditions. Resveratrol (RES) and polydatin (PD) are two kinds of natural phytoalexin with excellent antimicrobial and anti-inflammatory activity. In this study aim to evaluation the antiinflammatory ability of RES and PD on LPS-stimulate inflammatory cell model by Nitric oxide(NO) colorimetric method and NO synthases expression with qRT-PCR method, to provide a basis for the potential application and development in the future. The results showed that RES is significantly stronger than PD in NO synthases expression (P < 0.05). At the same time, the comparison of NO production inhibition rate between RES and PD are not significant (P > 0.05). RES and PD show their respective anti-inflammatory activity advantages under different indicators, which means we should choose RES or PD according to the different uses.

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Resveratrol differentially regulates NAMPT and SIRT1 in hepatocarcinoma cells and primary human hepatocytes

Cited by 3 publications

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SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells

SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells

Nicotinamide phosphoribosyl transferase regulates cell growth via the Sirt1/P53 signaling pathway and is a prognosis marker in colorectal cancer

Evaluation of Nitric Oxide Scavenging and Nitric Oxide Synthases Expression of Resveratrol and Polydatin

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