Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in breast cancer cell line

Yarmohamadi, Ahmad; Asadi, Jahanbakhsh; Gharaei, Roghaye; Mir, Mostafa; Khoshnazar, Alireza Khoshbin

doi:10.4103/jrcr.jrcr_37_17

Cited by 16 publications

(7 citation statements)

References 2 publications

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“…Different doses have been used. For instance, Van Nifterik et al (2012) used 0–2.5–5–7.5 mM, while Yarmohamadi et al (2018) used 0.5–64 mM for sensitizing cancer cells to radiation [29,30].…”

Section: Methodsmentioning

confidence: 99%

HDAC2 Inhibitor Valproic Acid Increases Radiation Sensitivity of Drug-Resistant Melanoma Cells

et al. 2019

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Resistance to anticancer drugs limits the effectiveness of chemotherapy in cancers. Melanoma cell lines B16F10C and A375C (parental) and B16F10R and A375R (drug-resistant sublines) were used to test radiation sensitization potential of valproic acid (VPA), an inhibitor of Histone deacetylase2 (HDAC2) and LDN193189 (BMP inhibitor). Inhibitors of other signaling pathways were tested for cross-resistance with the resistant cell lines. Cells were pretreated with low concentrations of VPA/ LDN193189 and exposed to 2 Gy radiation for radiation sensitization experiments. Assays-3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), live/dead, clonogenic, and melanin estimation were performed to test the effects of radiation sensitization. Interactions of VPA and HDAC2 were studied in silico. Dose-dependent growth inhibition was observed with all tested drugs. Radiation sensitization of melanoma cells with low dose of VPA induced synergistic cell death, decreased clonogenicity, and decreased melanin content. In silico docking showed two stable interactions between Arg39 of HDAC2 and VPA. In conclusion, pretreatment with low doses of VPA has a potential for sensitizing melanoma cells to low doses of radiation. The binding of VPA to HDAC2 reverses the drug resistance in melanoma and induces the cell death. Sensitization effects of VPA can be used for targeting drug-resistant cancers.

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Section: Methodsmentioning

confidence: 99%

HDAC2 Inhibitor Valproic Acid Increases Radiation Sensitivity of Drug-Resistant Melanoma Cells

et al. 2019

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“…17,18 Besides, t-loop hides the 3`end from telomerase and DNA repair activities and prevents from false activation of DNA repair types of machinery such as ataxia telangiectasia mutated (ATM) and Rad3-related protein (ATR) signalling pathways. [19][20][21] Telomeres are made up of G-quadruplex (G4). 22 Studies providing novel insights into G4 and G4related protein interactions have revealed a potential involvement of G4s in essential processes such as initiation of DNA replication and telomere maintenance.…”

Section: Organization and Function Of Telomeric Dnamentioning

confidence: 99%

<p>Shelterin Complex at Telomeres: Implications in Ageing</p>

Mir

Tehrani

Goodarzi

et al. 2020

CIA

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Different factors influence the development and control of ageing. It is well known that progressive telomere shorting is one of the molecular mechanisms underlying ageing. The shelterin complex consists of six telomere-specific proteins which are involved in the protection of chromosome ends. More particularly, this vital complex protects the telomeres from degradation, prevents from activation of unwanted repair systems, regulates the activity of telomerase, and has a crucial role in cellular senescent and ageing-related pathologies. This review explores the organization and function of telomeric DNA along with the mechanism of telomeres during ageing, followed by a discussion of the critical role of shelterin components and their changes during ageing.

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“…As far as HDI activity is concerned, VPA acts as an inhibitor of class I and IIa HDACs (5). Efficacy of VPA in this area can be defined by two different pathways, i.e., modulation of chromatin structure through intensification of histone acetylation and acetylation of non-histone proteins (3). Several studies suggest that VPA enhances DNA binding, inhibits cell proliferation and induces apoptosis (12).…”

Section: Valproic Acid and Its Hdi Activitymentioning

confidence: 99%

“…The most important is its high solubility both in water (sodium or magnesium salts) and lipids (an acidic form) which allows easy distribution of the drug throughout the body (1,2). Valproic acid, as a potent drug with a broad spectrum of antiseizure effects, has been used for the treatment of epilepsy as well as bipolar and migraine diseases for several decades (3). Moreover, VPA is not expensive and, due to its positive side-effect profile, is well tolerated by patients (1,4).…”

Section: Introductionmentioning

confidence: 99%

Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

2020

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Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy.

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Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in breast cancer cell line

Cited by 16 publications

References 2 publications

HDAC2 Inhibitor Valproic Acid Increases Radiation Sensitivity of Drug-Resistant Melanoma Cells

HDAC2 Inhibitor Valproic Acid Increases Radiation Sensitivity of Drug-Resistant Melanoma Cells

<p>Shelterin Complex at Telomeres: Implications in Ageing</p>

Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

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