Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

Dell’Omo, Giulia; Crescenti, Daniela; Vantaggiato, Cristina; Parravicini, Chiara; Borroni, Aurora P.; Rizzi, Nicoletta; Garofalo, Mariangela; Pinto, Andrea; Recordati, Camilla; Scanziani, Eugenio; Bassi, Fabio; Pruneri, Giancarlo; Conti, Paola; Eberini, Ivano; Maggi, Adriana; Ciana, Paolo

doi:10.1038/s41416-018-0372-7

Cited by 41 publications

(25 citation statements)

References 55 publications

(59 reference statements)

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“…Moreover, Gorski et al17 demonstrated that knockdown of SIRT1 inhibited the growth of cardiomyocytes. Inhibition of SIRT1 increased the activity of the tumor suppressor gene p53 and facilitated the expression of antiproliferative gene p21 18. In this study, miR-29a regulated the expression of SIRT1 by directly targeting to 3’-UTR of its mRNA in HeLa cells.…”

Section: Introductionmentioning

confidence: 55%

<p>MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis</p>

Peng

Niu

Wang

et al. 2019

OTT

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IntroductionCervical cancer is the second most frequently malignant tumors in females and metastasis is a challenge of the treatment of cervical cancer. MiR-29a is usually low expressed in several tumors and its functions in cervical cancer remain unclear.Patients and methodsThe quantitative real-time polymerase chain reaction was employed to assess the expression of miR-29a and the Sirtuin-1 (SIRT1). Cell metastatic ability was assessed using Transwell and Western blot assays. The dual-luciferase reporter assay was performed to verify that miR-29a targeted to the 3’-untranslated region (UTR) of SIRT1 mRNA.ResultsMiR-29a was low expressed in cervical cancer and downregulation of miR-29a was associated with poor outcome. MiR-29a regulated the expression of SIRT1 by targeting to its 3’-UTR of mRNA in HeLa cells. SIRT1 was upregulated in cervical cancer tissues and cells in comparison with the non-tumor tissues and normal cells. Upregulation of SIRT1 predicted worse outcome of cervical cancer patients. MiR-29a was participated in the migration, invasion and epithelial–mesenchymal transition (EMT) in cervical cancer through directly targeting to the 3’-UTR of SIRT1 mRNA. SIRT1 reversed partial roles of miR-29a on metastasis in cervical cancer.ConclusionmiR-29a suppressed migration, invasion and EMT by directly targeting to SIRT1 in cervical cancer. The newly identified miR-29a/SIRT1 axis provides novel insight into the pathogenesis of cervical cancer.

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Section: Introductionmentioning

confidence: 55%

<p>MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis</p>

Peng

Niu

Wang

et al. 2019

OTT

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“…The trans-viniferin species and enantiomeric form database was sketched and prepared with the LigPrep, carefully checking the stereocenters. Molecular docking was carried out through the Glide Ligand Docking with a standard precision (SP) according to a well-established protocol [31]. The active site was identified through the Site Map tool and confirmed according to the annotations of the UniProt pig pancreatic alpha amylase entry (AMYP_PIG).…”

Section: Computational Proceduresmentioning

confidence: 99%

Inhibition of Pancreatic α-amylase by Resveratrol Derivatives: Biological Activity and Molecular Modelling Evidence for Cooperativity between Viniferin Enantiomers

et al. 2019

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To improve the current understanding of the role of stilbenoids in the management of diabetes, the inhibition of the pancreatic α-amylase by resveratrol derivatives was investigated. To approach in a systematic way, the mechanistic and structural aspects of the interaction, potential bioactive agents were prepared as single molecules, that were used for the biological evaluation of the determinants of inhibitory binding. Some dimeric stilbenoids—in particular, viniferin isomers— were found to be better than the reference drug acarbose in inhibiting the pancreatic α-amylase. Racemic mixtures of viniferins were more effective inhibitors than the respective isolated pure enantiomers at an equivalent total concentration, and displayed cooperative effects not observed with the individual enantiomers. The molecular docking analysis provided a thermodynamics-based rationale for the measured inhibitory ability and for the observed synergistic effects. Indeed, the binding of additional ligands on the surface of the alpha-amylase was found to decrease the dissociation constant of inhibitors bound to the active site of the enzyme, thus providing a mechanistic rationale for the observed inhibitory synergies.

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“…In a work published in 2019 by Dell'Omo et al of the Milan group, the ability of NSAIDs to determine the inhibition of proinflammatory factors and the activation of the anti-oncogenic p53 / p21 pathway was studied. This study suggests a new strategy for the design of anticancer drugs, through the modulation of the pro-inflammatory cascade [18]. In a retrospective study published in 2018 Desmedt et al show that the intra-operative administration of ketorolac during breast conservative surgery is statistically significantly associated with a reduction of distant recurrences in patients with early breast cancer and increased BMI [19].…”

Section: Iort Delivered With Xoft® Axxent® Ebx™mentioning

confidence: 84%

Overview on the Role of Breast Conservative Treatments for Early Breast Cancer with Low Risk of Recurrence: History, Standard and Controversies

Fabbri¹,

M²,

Carcoforo³

2019

IJCG

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The HistoryOne third of breast cancer cases occurs in patients over the age of 65 years, and in more developed countries this proportion rises to more than 47% after 70 years according to the updated Surveillance, Epidemiology, and End Results (SEER) database [1]. AbstractBackground: breast-conserving therapy is the mainstay for early-stage breast cancer, but this concept required a long process because comprehension of tumor biology was first necessary. In the last century several studies conducted to a progressive limitation of surgery and a progressive increase of complementary therapy, thanks to the early diagnosis of the screening in high-risk groups. The radiotherapy of the whole breast remains the gold standard after quadrantectomy, but new technical devices are leading to a modification of this approach. The advantage of breast conservative therapy is a conserved quality of life, but principal questions remain on the long term effects of these therapies and the risk of recurrences. Methods:We conducted an overview on the breast-conserving therapy for early-stage breast cancer with low risk of recurrences searching articles in the Pubmed literature with care on the role of intraoperative radiotherapy.Conclusions: nowadays it become important to establish a correct therapeutic timing, adapting it to the characteristics of the individual patient and to the biology of the tumor. Radiotherapy and chemotherapy programs should be able to embrace according to modulable times and take into account the differences of each individual case. The reduction of post actinic toxicity represents an objective to be pursued, also for the possible overlap with the toxicity of the chemotherapeutic treatment and in this a fundamental role could be played by IORT. Moreover, considering the increase in patient survival that will inevitably lead to an increase in local recurrences, the possibility of a re-irradiation will be more and more frequent. Recent studies on the modulation of inflammation factors induced by the use of drugs during surgery could lead to new considerations on chemotherapy treatment. In conclusion, It could be useful to limit the field of action of complementary treatments for selected patients, like in the past it was proposed for surgical treatment, to allow any future therapy or reinterventions in case of recurrences, even with reconstructive intent.Keywords: Intraoperative radiotherapy (IORT), breast conservative surgery (BCS), accelerated partial breast irradiation (APBI).Fabbri Nicolò et al.

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Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

Cited by 41 publications

References 55 publications

<p>MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis</p>

<p>MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis</p>

Inhibition of Pancreatic α-amylase by Resveratrol Derivatives: Biological Activity and Molecular Modelling Evidence for Cooperativity between Viniferin Enantiomers

Overview on the Role of Breast Conservative Treatments for Early Breast Cancer with Low Risk of Recurrence: History, Standard and Controversies

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