Effect of 5-aza-2'-deoxycytidine in comparison to valproic acid and trichostatin A on histone deacetylase 1, DNA methyltransferase 1, and CIP/KIP family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer SW480 cell line

Sanaei, Masumeh; Kavoosi, Fraidoon

doi:10.4103/abr.abr_91_19

Cited by 25 publications

(13 citation statements)

References 48 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, overexpressed DNMT1 was found both in OSCC cells and clinical specimens [ 47 , 48 ], suggesting the functional role of DNMT1 in OSCC cells. A previous study showed that treatment of 5-AZA-2′-deoxycytidine (5-AZA-CdR) causes a decreased DNMT1 expression and increased p21 expression in colon cancer SW480 cells [ 49 ]. Our data clearly show that statins functioned as 5-AZA to suppress DNMT1 expression and promoted p21 expression in OSCC cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells

Dongoran

Wang

Lin

et al. 2020

Cancers

View full text Add to dashboard Cite

Statins, also known as HMG-CoA reductase inhibitors, are a class of cholesterol-lowering drugs and their anti-cancer effects have been studied in different types of malignant diseases. In the present study, we investigated the anti-proliferative effects of statins, including cerivastatin and simvastatin, on oral squamous cell carcinoma (OSCC) cells. Our data showed that statins inhibited the proliferation of three OSCC cell lines in a dose-dependent manner and this growth inhibition was confirmed through G0/G1 cell cycle arrest. Accordingly, we found the upregulation of p21 and downregulation of cyclin-dependent kinases, including CDK2, CDK4, and CDK6, in the statin-treated cells. Importantly, we clearly showed that statins were able to inhibit the expression of DNA methyltransferase 1 (DNMT1) and further promote the expression of p21. Taken together, our data demonstrated that the anti-proliferative effect of statins is mediated by suppressing DNMT1 expression, thus promoting p21 expression and leading to G0/G1 cell cycle arrest in OSCC cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells

Dongoran

Wang

Lin

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Gene expression deregulation by VPA has been widely investigated over the last few decades (Marchion et al, 2005;Jergil et al, 2009Jergil et al, , 2011Chiu et al, 2013;Shinde et al, 2016;Balasubramanian et al, 2019;Kotajima-Murakami et al, 2019;Lin et al, 2019;Sanaei and Kavoosi, 2019). Interestingly, some of the causative genes of the aforementioned syndromes are dysregulated in different experimental models.…”

Section: Shared Epigenetic and Gene Expression Alterationsmentioning

confidence: 99%

Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies

Parodi

Fede

Peron

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Prenatal exposure to valproate (VPA), an antiepileptic drug, has been associated with fetal valproate spectrum disorders (FVSD), a clinical condition including congenital malformations, developmental delay, intellectual disability as well as autism spectrum disorder, together with a distinctive facial appearance. VPA is a known inhibitor of histone deacetylase which regulates the chromatin state. Interestingly, perturbations of this epigenetic balance are associated with chromatinopathies, a heterogeneous group of Mendelian disorders arising from mutations in components of the epigenetic machinery. Patients affected from these disorders display a plethora of clinical signs, mainly neurological deficits and intellectual disability, together with distinctive craniofacial dysmorphisms. Remarkably, critically examining the phenotype of FVSD and chromatinopathies, they shared several overlapping features that can be observed despite the different etiologies of these disorders, suggesting the possible existence of a common perturbed mechanism(s) during embryonic development.

show abstract

“…TSA inhibits HDAC activity [69], downregulates HDAC1 expression [75], increases histone H4 [69] and estrogen receptor (ER) acetylation in breast cancer cell lines [76], increases histone H3 lysine 9 and lysine 27 acetylation [76] and upregulates p21, p27 and p57 expression in colon cancer cell lines [75] Additionally, in PCa, TSA increases histone H4 lysine 16 acetylation, particularly in CRPC cell lines [73], and affects p53 acetylation [49]. In addition, TSA presents nonepigenetic effects, including decreased cell proliferation [68,74], increased cell death [72,75] with an increase in active caspase-3 levels [71], increased hypoxic responses [74], downregulation of cyclin D1 gene expression [71], cell cycle arrest at G 1 phase, increased expression of Bax gene and downregulated Bcl-2 gene expression and decreased phosphorylation of Akt and ERK proteins [70]. There is an ongoing clinical trial (NCT03838926) recruiting patients with hematological malignancies to investigate the anticancer effectiveness of TSA.…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?

et al. 2020

View full text Add to dashboard Cite

Epigenetic alterations, as a cancer hallmark, are associated with cancer initiation, progression and aggressiveness. Considering, however, that these alterations are reversible, drugs that target epigenetic machinery may have an inhibitory effect upon cancer treatment. The traditional drug discovery pathway is time-consuming and expensive, and thus, new and more effective strategies are required. Drug Repurposing (DR) comprises the discovery of a new medical indication for a drug that is approved for another indication, which has been recalled, that was not accepted or failed to prove efficacy. DR presents several advantages, mainly reduced resources, absence of the initial target discovery process and the reduced time necessary for the drug to be commercially available. There are numerous old drugs that are under study as repurposed epigenetic inhibitors which have demonstrated promising results in in vitro tumor models. Herein, we summarize the DR process and explore several repurposed drugs with different epigenetic targets that constitute promising candidates for cancer treatment, highlighting their mechanisms of action.

show abstract

Effect of 5-aza-2'-deoxycytidine in comparison to valproic acid and trichostatin A on histone deacetylase 1, DNA methyltransferase 1, and CIP/KIP family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer SW480 cell line

Cited by 25 publications

References 48 publications

Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells

Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells

Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies

Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?

Contact Info

Product

Resources

About