Dataset Information

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666-1 cells through regulating PARP-2/SIRT1/AMPK signaling pathway.

ABSTRACT: Background/Aim:Nobiletin, a major polymethoxyflavones (PMFs) from citri reticulatae pericarpium (CRP), can inhibit several forms of cancer proliferation. However, the effects of nobiletin on nasopharyngeal carcinoma (NPC) C666-1 cells remain largely unknown. Materials and Methods:Cell counting kit 8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the apoptosis rate. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were applied to determine the expression of mRNA and protein, respectively. Results:We showed that the proliferation rate of C666-1 cells was inhibited and the apoptosis rate was raised after treating with nobiletin. Moreover, nobiletin inhibited the expression of poly(ADP-ribose)polymerase-2 (PARP-2), and the tumor suppression effect of nobiletin on C666-1 is associated with PARP-2-dependent pathway. Conclusion:We demonstrated for the first time that nobiletin inhibited the growth of C666-1 cells, which may be relative to its regulation on PARP-2/SIRT1/AMPK signaling pathway. Our result implied that nobiletin may serve as a strategy to treat nasopharyngeal carcinoma.

SUBMITTER: Zheng GD

PROVIDER: S-EPMC6418462 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666-1 cells through regulating PARP-2/SIRT1/AMPK signaling pathway.

Zheng Guo Dong GD Hu Ping Jun PJ Chao Ying Xin YX Zhou Ying Y Yang Xiu Juan XJ Chen Bai Zhong BZ Yu Xi Yong XY Cai Yi Y

Food science & nutrition 20190210 3

<h4>Background/aim</h4>Nobiletin, a major polymethoxyflavones (PMFs) from citri reticulatae pericarpium (CRP), can inhibit several forms of cancer proliferation. However, the effects of nobiletin on nasopharyngeal carcinoma (NPC) C666-1 cells remain largely unknown.<h4>Materials and methods</h4>Cell counting kit 8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the apoptosis rate. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot ...[more]

PMID: 30918653

Similar Datasets

Project description:Nicotinamide adenine dinucleotide (NAD+) -dependent protein deacetylase SIRT1 plays an important role in the regulation of metabolism. Although the administration of nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to ameliorate metabolic disorders, such as insulin resistance and glucose intolerance, the direct effect of NMN on the regulation of lipid metabolism in adipocytes remains unclear. We here investigated the effect of NMN on lipid storage in 3T3-L1 differentiated adipocytes. Oil-red O staining showed that NMN treatment reduced lipid accumulation in these cells. NMN was found to enhance lipolysis in adipocytes since the concentration of glycerol in the media was increased by NMN treatment. Western blotting and real-time RT-PCR analysis revealed that adipose triglyceride lipase (ATGL) expression at both protein and mRNA level was increased with NMN treatment in 3T3-L1 adipocytes. Whereas NMN increased SIRT1 expression and AMPK activation, an AMPK inhibitor compound C restored the NMN-dependent upregulation of ATGL expression in these cells, suggesting that NMN upregulates ATGL expression through the SIRT1-AMPK axis. NMN administration significantly decreased subcutaneous fat mass in mice on a high-fat diet. We also found that adipocyte size in subcutaneous fat was decreased with NMN treatment. Consistent with the alteration of fat mass and adipocyte size, the ATGL expression in subcutaneous fat was slightly, albeit significantly, increased with NMN treatment. These results indicate that NMN suppresses subcutaneous fat mass in diet-induced obese mice, potentially in part via the upregulation of ATGL. Unexpectedly, the reduction in fat mass as well as ATGL upregulation with NMN treatment were not observed in epididymal fat, implying that the effects of NMN are site-specific in adipose tissue. Thus, these findings provide important insights into the mechanism of NMN/NAD+ in the regulation of metabolism. Highlights • NMN induces lipolysis by increasing ATGL expression in 3T3-L1 adipocytes.• NMN enhances ATGL expression through SIRT1/AMPK axis in 3T3-L1 adipocytes.• NMN ameliorates diet-induced obesity in mice by suppressing adipocyte hypertrophy.

Project description:BackgroundSalvia-Nelumbinis naturalis (SNN), the extract of Chinese herbal medicine, has shown effects on NAFLD. This study aims to explore the underlying mechanism of SNN for regulating the lipid metabolism disorder in NAFLD based on the SIRT1/AMPK signaling pathway.MethodsMale C57BL/6J mice fed with a high-fat diet (HFD) were used to establish the NAFLD model. Dynamic changes of mice including body weight, liver weight, serological biochemical indexes, liver histopathological changes, and protein level of AMPK and SIRT1 were monitored. After18 weeks, SNN treatment was administrated to the NAFLD mice for another 4 weeks. Besides the aforementioned indices, TC and TG of liver tissues were also measured. Western blot and quantitative RT-PCR were used to detect the expression and/or activation of SIRT1 and AMPK, as well as the molecules associated with lipid synthesis and β-oxidation. Furthermore, AML12 cells with lipid accumulation induced by fatty acids were treated with LZG and EX527 (SIRT1 inhibitor) or Compound C (AMPK inhibitor ) to confirm the potential pharmacological mechanism.ResultsDynamic observation found the mice induced by HFD with gradually increased body and liver weight, elevated serum cholesterol, hepatic lipid accumulation, and liver injury. After 16 weeks, these indicators have shown obvious changes. Additionally, the hepatic level of SIRT1 and AMPK activation was identified gradually decreased with NAFLD progress. The mice with SNN administration had lower body weight, liver weight, and serum level of LDL-c and ALT than those of the NAFLD model. Hepatosteatosis and hepatic TG content in the liver tissues of the SNN group were significantly reduced. When compared with control mice, the NAFLD mice had significantly decreased hepatic expression of SIRT1, p-AMPK, p-ACC, ACOX1, and increased total Acetylated-lysine, SUV39H2, and SREBP-1c. The administration of SNN reversed the expression of these molecules. In vitro experiments showed the effect of SNN in ameliorating hepatosteatosis and regulating the expression of lipid metabolism-related genes in AML12 cells, which were diminished by EX527 or Compound C co-incubation.ConclusionsTaken together, the SIRT1/AMPK signaling pathway, involved in hepatic lipid synthesis and degradation, plays a pivotal role in the pathogenesis of NAFLD development. The regulation of SIRT1/AMPK signaling greatly contributes to the underlying therapeutic mechanism of SNN for NAFLD.

Project description:Increasing evidence reveals that estrogen, especially 17β-estradiol (17β-E2), is associated with articular cartilage metabolism disorder and postmenopausal osteoarthritis (OA). SIRT1, AMPK, and mTOR are regarded as critical mitophagy regulators. Recent studies have shown that mitophagy displays a protective effect against OA, but the molecular mechanism is not well known. This study aimed to investigate the effect of 17β-E2 on Sirtuin-1 (SIRT1) expression and the induction of mitophagy upregulation by 17β-E2 via the SIRT1-mediated AMP-activated protein kinase (AMPK)/mammalian target of the rapamycin (mTOR) signaling pathway to protect chondrocytes. ATDC5 chondrocytes were treated with different concentrations of 17β-E2 (0 M, 1 × 10-9 M, 1 × 10-8 M, and 1 × 10-7 M) for 24 h or pretreatment with or without NAM (SIRT1 inhibitor), Compound C (AMPK inhibitor) and S1842 (mTOR inhibitor) for 30 min prior to treatment with 17β-E2 (1 × 10-7 M) for 24 in each groups. Expression of SIRT1 was evaluated by real-time PCR, Western blotting and confocal immunofluorescence staining. Then, the mitophagosomes in cells were observed under a transmission electron microscopy (TEM), and the AMPK/mTOR signaling pathway was detected by Western blotting. The mitophagy-related proteins, p-AMPK, p-mTOR, p-JNK, and p-p38 were also identified by Western blot analysis. The chondrocytes viability and proliferation were determined by MTT and 5-Bromo-2'-deoxyuridine (BrdU) assay. These experiments were independently repeated 3 times The study found that 17β-E2 increased the expression level of SIRT1, p-AMPK, and mitophagy-related proteins but decreased p-mTOR expression, and then induced mitophagy upregulation in chondrocytes. More mitochondrial autophagosomes were observed in 17β-E2-treated chondrocytes under a transmission electron microscope. Also, 17β-E2 improved cell viability and proliferation with the higher expression of SIRT1 and activation of the AMPK/mTOR signaling pathway. However, SIRT1 inhibitor nicotinamide (NAM) and AMPK inhibitor Compound C blocked the beneficial effect of 17β-E2. In summary, this study was novel in demonstrating that 17β-E2 induced mitophagy upregulation to protect chondrocytes via the SIRT1-mediated AMPK/mTOR signaling pathway.

Dataset Information

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666-1 cells through regulating PARP-2/SIRT1/AMPK signaling pathway.

Publications

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666-1 cells through regulating PARP-2/SIRT1/AMPK signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets