Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines

Catalano, Maria Graziella; Poli, Roberta; Pugliese, Mariateresa; Fortunati, Nicoletta; Boccuzzi, Giuseppe

doi:10.1677/erc-07-0096

Cited by 75 publications

(56 citation statements)

References 28 publications

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“…VPA increases the toxic effects of paclitaxel in anaplastic thyroid carcinoma cells due to their interaction with the tubulin β subunit. VPA enhances tubulin hyperacetylation that stabilizes microtubule structures 70 . Similar enhancement of apoptosis was observed in endometrial carcinoma cells treated with trichostatin A and paclitaxel caused by the activation of the intrinsic mitochondria-dependent pathway.…”

Section: ) Promising Results Have Been Reported For Combinations Of mentioning

confidence: 99%

Histone deacetylase inhibitors in cancer therapy. A review

Hraběta¹,

Stiborová²,

Adam³

et al. 2014

BIOMED PAP

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a Background. Despite recent success toward discovery of more effective anticancer drugs, chemoresistance remains a major cause of treatment failure. There is emerging evidence that epigenetics plays a key role in the development of the resistance. Epigenetic regulators such as histone acetyltransferases (HATs) and histone deacetylases (HDACs) play an important role in gene expression. The latter are found to be commonly linked with many types of cancers and influence cancer development. Overall, histone acetylation is being investigated as a therapeutic target because of its importance in regulating gene expression. This review summarizes mechanisms of the anticancer effects of histone deacetylase (HDAC) inhibitors and the results of clinical studies. Results. Different HDAC inhibitors induce cancer cell death by different mechanisms that include changes in gene expression and alteration of both histone and non-histone proteins. Enhanced histone acetylation in tumors results in modification of expression of genes involved in cell signaling. Inhibition of HDACs causes changed expression in 2-10 % of genes involved in important biological processes. The results of experiments and clinical studies demonstrate that combination of HDAC inhibitors with some anticancer drugs have synergistic or additive effects. Conclusions. Even though many biological effects of HDAC inhibitors have been found, most of the mechanisms of their action remain unclear. In addition, their use in combination with other drugs and the combination regime need to be investigated. The discovery of predictive factors is also necessary. Finally, a key question is whether the pan-HDAC inhibitors or the selective inhibitors will be more efficient for different types of cancers.

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Section: ) Promising Results Have Been Reported For Combinations Of mentioning

confidence: 99%

Histone deacetylase inhibitors in cancer therapy. A review

Hraběta¹,

Stiborová²,

Adam³

et al. 2014

BIOMED PAP

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“…Recent studies have shown that HDACis have the potential to inhibit carcinogenesis and fibrogenesis (2,(9)(10)(11)(12)(13)(14)(15). VPA, a semiselective HDACi (20), is widely prescribed for patients with epilepsy and psychiatric disorders and well tolerated by the majority of patients (21,22).…”

Section: Discussionmentioning

confidence: 99%

“…Histone acetylation and deacetylation is controlled by histone acetyltransferases and histone deacetylases. In recent years, histone deacetylase inhibitors (HDACis) showed anti-cancer activities and are, therefore, of clinical interest (9)(10)(11)(12). There are also several reports showing an antifibrogenic effect of HDACis, but the underlying mechanism is still unclear (2,(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line

et al. 2011

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Abstract. Histone acetylation and deacetylation have been thought to be related to gene expression, and there are many reports indicating that histone deacetylase inhibitors (HDACis) exert antifibrogenic effects in several organs. In injured livers, hepatic stellate cells (HSCs) are activated in response to profibrogenic mediators and produce large amounts of extracellular matrix. In particular, transforming growth factor-β1 (TGF-β1) is considered as a key factor in accelerating hepatic fibrosis because it is released from activated HSCs and further stimulates them. The present study aimed to clarify whether sodium valproate (VPA) has suppressive effects on cultured human HSCs (LI90). We showed that treatment with VPA had no significantly suppressive effect on cell proliferation at a concentration of 1 mM, which corresponded approximately to the serum concentration obtained by the administration of a clinical dose. However, VPA prevented the morphological changes characteristic for activation and inhibited the expression of collagen type 1 α1 (COL1A1) and TGF-β1 in activated LI90 cells at the mRNA and protein levels. Our results support the hypothesis that VPA exerts antifibrogenic activity with little cytotoxicity at 1 mM, and HDACis are expected to be used in clinical practice for the treatment of fibrotic diseases. IntroductionHepatic stellate cells (HSCs) are considered as the main source of extracellular matrix (ECM) proteins in chronic liver diseases leading to fibrosis. In a normal liver, these cells are liver-specific pericytes that serve as major vitamin A storage sites and show little proliferative activity (1). In an injured liver, however, HSCs undergo phenotypic changes termed activation in response to profibrogenic mediators such as platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), endothelin (ET)-1, and members of the transforming growth factor-β (TGF-β) family. During this phenotypic transition, HSCs express α smooth muscle actin (αSMA) and acquire the capacity to proliferate and produce excessive quantities of ECM proteins (2,3). It is reported that TGF-β and its intracellular mediators, i.e., Smad proteins, play important roles in stimulating collagen synthesis. In particular, production of TGF-β1 is enhanced by activated HSCs, and it has been considered that the effects of TGF-β1 on HSCs involve predominantly autocrine stimulation (4,5). Therefore, inhibition of TGF-β1 signals seems to be a potential target for therapeutic intervention in patients with liver fibrosis.It is considered that histone modification, particularly histone acetylation, is a key principle of epigenetic regulation of gene expression (6-8). Histone acetylation and deacetylation is controlled by histone acetyltransferases and histone deacetylases. In recent years, histone deacetylase inhibitors (HDACis) showed anti-cancer activities and are, therefore, of clinical interest (9-12). There are also several reports showing an antifibrogenic effect of HDACis, but the underlying mechanism is still un...

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“…Multi-disciplinary treatments including radio-and chemotherapy poorly control the progression of this disease and patients rarely survive >1 year after initial diagnosis (1). Novel strategies to control this lethal malignancy are therefore mandatory (2,3). Imatinib mesylate is a molecular target agent that suppresses signal transduction pathways mediated through c-Abl, c-kit, and platelet-derived growth factor receptors (PDGFRs) (4).…”

Section: Introductionmentioning

confidence: 99%

“…Reinforcement of the killing activity of drugs targeting DNA (2,14,15) and tubulin (3) has been reported for histone deacetylase inhibitors (HDIs), a potent class of antineoplastic agents. These drugs induce differentiation, growth arrest and apoptosis of transformed cells (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

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

Catalano

Pugliese²,

Poli³

et al. 2009

Oncol Rep

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Abstract. New therapeutic approaches are mandatory for anaplastic thyroid cancer. We investigated the ability of a new combined treatment using valproic acid (VPA), the only clinically available histone deacetylase inhibitor, and the tyrosine-kinase inhibitor imatinib mesylate to control the cell growth of anaplastic thyroid cancer cell lines. We showed that treatment with imatinib alone is unable to affect the cell growth of anaplastic thyroid cancer cells, whereas in ARO cells, the combined treatment resulted in a cytostatic effect, with clinically achievable doses of imatinib and VPA. The effect is mediated by G 1 growth arrest, acting through p21 expression and the impairment of AKT phosphorylation.

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Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines

Cited by 75 publications

References 28 publications

Histone deacetylase inhibitors in cancer therapy. A review

Histone deacetylase inhibitors in cancer therapy. A review

Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line

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

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