Effects of the histone deacetylase inhibitor valproic acid on the sensitivity of anaplastic thyroid cancer cell lines to imatinib

Catalano, Maria Graziella; Pugliese, Mariateresa; Poli, Roberta; Bosco, Ornella; Bertieri, Raffaello; Fortunati, Nicoletta; Boccuzzi, Giuseppe

doi:10.3892/or_00000252

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…One study found that treatment with imatinib alone was not able to grow anaplastic cells in thyroid cancer cells, but that combination therapy (imatinib and VPA) had a cytostatic effect. This effect is mediated by stunted G1 growth and acts through p21 expression and impaired AKT phosphorylation [45].…”

Section: Discussionmentioning

confidence: 99%

Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

et al. 2021

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Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland.More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients' lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not su cient in the treatment of ATC, so alternative therapies are needed. The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, Effect of VPA on miRNAs affecting histone deacetylase were determined by Quantitative RT-PCR. In BRAFV600E / mut SW1736 (SW1736) cell line IC50 dose for VPA found 1.6 mg/ml. in our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes is miR- 323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101-5p increased signi cantly. VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). We got very promising results with VPA.

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Section: Discussionmentioning

confidence: 99%

Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

et al. 2021

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A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin

et al. 2016

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Summary Objective Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer. Design An open-label Simon two-stage phase II trial. Patients and Measurements VA was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid–stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake. Results Thirteen patients with a median age of 66 years (50–78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hürthle cell carcinoma. None of the 10 patients who completed the 10-week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression, and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression. Conclusions VA does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin.

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Hyperglycemia Promotes Chemoresistance Through the Reduction of the Mitochondrial DNA Damage, the Bax/Bcl-2 and Bax/Bcl-XL Ratio, and the Cells in Sub-G1 Phase Due to Antitumoral Drugs Induced-Cytotoxicity in Human Colon Adenocarcinoma Cells

et al. 2018

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Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies clearly indicate that the risk of several types of cancer is increased in diabetic patients and a number of cancer types have shown a higher mortality rate in patients with hyperglycemic associated pathologies. This scenario could be due, at least in part, to a lower efficacy of the cancer treatments which needs to be better investigated. Here, we evaluated the effects of a prolonged exposure to high glucose (HG) to the response to chemotherapy on human colon adenocarcinoma HT29 and LOVO cell lines. We observed that hyperglycemia protected against the decreased cell viability and cytotoxicity and preserved from the mitochondrial DNA lesions induced by doxorubicin (DOX) and 5-fluorouracil (5-FU) treatments by lowering ROS production. In HT29 cells the amount of intracellular DOX and its nuclear localization were not modified by HG incubation in terms of Pgp, BCRP, MRP1, 5 and 8 activity and gene expression. On the contrary, in LOVO cells, the amount of intracellular DOX was significantly decreased after a bolus of DOX in HG condition and the expression and activity of MPR1 was increased, suggesting that HG promotes drug chemoresistance in both HT29 and LOVO cells, but in a different way. In both cell types, HG condition prevented the susceptibility to apoptosis by decreasing the ratio Bax/Bcl-2 and Bax/Bcl-XL and diminished the level of cytosolic cytochrome c and the cleavage of full length of PARP induced by DOX and 5-FU. Finally, hyperglycemia reduced cell death by decreasing the cell percentage in sub-G1 peak induced by DOX (via a cell cycle arrest in the G2/M phase) and 5-FU (via a cell cycle arrest in the S phase) in HT29 and LOVO cells. Taken together, our data showed that a prolonged exposure to HG protects human colon adenocarcinoma cells from the cytotoxic effects of two widely used chemotherapeutic drugs, impairing the effectiveness of the chemotherapy itself.

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Effects of the histone deacetylase inhibitor valproic acid on the sensitivity of anaplastic thyroid cancer cell lines to imatinib

Cited by 3 publications

References 22 publications

Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin

Hyperglycemia Promotes Chemoresistance Through the Reduction of the Mitochondrial DNA Damage, the Bax/Bcl-2 and Bax/Bcl-XL Ratio, and the Cells in Sub-G1 Phase Due to Antitumoral Drugs Induced-Cytotoxicity in Human Colon Adenocarcinoma Cells

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