Effect of sodium butyrate on doxorubicin resistance and expression of multidrug resistance genes in thyroid carcinoma cells

Massart, Catherine; Poirier, Charles; Fergelot, Patricia; Fardel, Olivier; Gibassier, J

doi:10.1097/00001813-200503000-00004

Cited by 18 publications

(15 citation statements)

References 22 publications

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“…Notably, cells treated with sodium butyrate are exposed to 100-fold higher drug levels (f20 nmol/L depsipeptide versus 2 mmol/L sodium butyrate) and this may result in other cellular effects aside from histone acetylation. Other groups have shown that sodium butyrate potentiates doxorubicin cytotoxicity independent of the expression of ABC transporters, such as Pgp (37,38). Interestingly, when SW620 cells were treated with sodium butyrate, we noted that the increased surface Pgp expression was accompanied by increased transport of rhodamine 123, a substrate not tested in the original study (data not shown).…”

Section: Discussionmentioning

confidence: 52%

Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176)

Robey

Zhan

Piekarz

et al. 2006

Clinical Cancer Research

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The increased expression of markers associated with a differentiated phenotype, such as P-glycoprotein (Pgp), follows treatment with histone deacetylase inhibitors. Because depsipeptide (FR901228, FK228, NSC630176) is a substrate for Pgp, up-regulation of the gene that encodes it, MDR1, would mean that depsipeptide induces its own mechanism of resistance. To examine the effect of depsipeptide on expression of ATP-binding cassette transporters associated with multidrug resistance, the kidney cancer cell lines 108, 121, 127, and 143 were treated with depsipeptide and evaluated by quantitative reverse transcription-PCR. Increased levels of MDR1 (1.3-to 6.3-fold) and ABCG2 (3.2-to 11.1-fold) but not MRP1 (0.9-to 1.3-fold) were observed. The induced Pgp transported the fluorescent substrates rhodamine 123, bisantrene, calcein-AM, BODIPY-vinblastine, and BODIPY-paclitaxel. In normal peripheral blood mononuclear cells (PBMC) and circulating tumor cells obtained from patients receiving depsipeptide, increased levels of histone H3 acetylation were found. We next examined MDR1 levels in normal and malignant PBMCs obtained from 15 patients enrolled in clinical trials with depsipeptide and detected up to a 6-fold increase in normal PBMCs and up to an 8-fold increase in circulating tumor cells after depsipeptide administration. In one patient with Sé zary syndrome, increased MDR1 gene expression was accompanied by increased cell surface Pgp expression in circulating Sézary cells as determined by measurement of MRK-16 staining by flow cytometry.These studies suggest that depsipeptide induces its own mechanism of resistance and thus provide a basis for clinical trials evaluating depsipeptide in combination with a Pgp inhibitor.

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Section: Discussionmentioning

confidence: 52%

Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176)

Robey

Zhan

Piekarz

et al. 2006

Clinical Cancer Research

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“…7 mM, which is without any serious side effects and corresponds to the plasma levels reached in patients treated for epilepsy. Previous reports show that other HDAC inhibitors, such as trichostatin A (Greenberg et al 2001a), sodium butyrate (Greenberg et al 2001b), and suberoyl anilide hydroxamic acid (SAHA) (Mitsiades et al 2005) are able to suppress cell growth of thyroid cancer cell lines and sensitize them to cytotoxic chemotherapy (Massart et al 2005, Mitsiades et al 2005, Rho et al 2005, but the side effects of these drugs are still under evaluation.…”

Section: Discussionmentioning

confidence: 99%

Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells

Catalano¹,

Fortunati²,

Pugliese³

et al. 2006

Journal of Endocrinology

109

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Multimodality treatments (i.e. surgery, chemotherapy, and radiotherapy) are recommended for anaplastic thyroid carcinoma (ATC), an extremely lethal human cancer, but to date there is little evidence that such approaches improve survival rates. It is thus necessary to seek new therapeutic tools. Histone deacetylase (HDAC) inhibitors are a promising class of antineoplastic agents that induce differentiation and apoptosis. Moreover, they may enhance the cytotoxicity of drugs targeting DNA through acetylation of histones. Using two ATC cell lines (CAL-62 and ARO), we show here that valproic acid (VPA), a clinically available HDAC inhibitor, enhances the activity of doxorubicin, whose anti-tumor properties involve binding to DNA and inhibiting topoisomerase II. A meager 0 . 7 mM VPA, which corresponds to serum concentrations in patients treated for epilepsy, is able to increase the cytotoxicity of doxorubicin about threefold in CAL-62 cells and twofold in ARO cells. The sensitizing effect, which is through histone acetylation, involves increased apoptosis, which is also shown by the increased caspase 3 activation and the enhancement of doxorubicin-induced G 2 cell cycle arrest. These results might offer a rationale for clinical studies of a new combined therapy in an effort to improve the outcome of patients with anaplastic thyroid cancer.

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“…The IEC-6 cell line was obtained from Deutsche Sammlung von Mikroorganismen und Zellkulturen (ACC-111, Braunschweig, Germany) and was used between passage numbers [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. The cells were maintained in a humidified atmosphere of 5% CO 2-95% air and were cultured in Dulbecco's Modified Eagle's Medium:RPMI 1640 medium (1:1), supplemented with 10% fetal bovine serum, 0.1 U/ml insulin, 5.96 g HEPES, 2.2 g NaHCO 3, 100 U/ml penicillin, 100 g/ml streptomycin, and 0.25 g/ml amphotericin B (all from Sigma).…”

Section: Iec-6 Cell Culturementioning

confidence: 99%

“…16,50). Interestingly enough, BT is known to induce the expression of MDR1 (17,43,44). Moreover, other histone deacetylase inhibitors such as depsipeptide (71), vorinostat, valproic acid (19), and trichostatin A (37) also induce MDR1-dependent resistance in human cancer cells, and depsipeptide and trichostatin A were described as MDR1 substrates (54, 73).…”

mentioning

confidence: 99%

The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein

Gonçalves

Gregório

Martel

2011

American Journal of Physiology-Cell Physiology

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Gonçalves P, Gregório I, Martel F. The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein. Am J Physiol Cell Physiol 301: C984 -C994, 2011. First published July 20, 2011 doi:10.1152/ajpcell.00146.2011.-Colorectal cancer is one of the most common cancers worldwide. Butyrate (BT) plays a key role in colonic epithelium homeostasis. The aim of this work was to investigate the possibility of BT being transported by P-glycoprotein (MDR1), multidrug resistance proteins (MRPs), or breast cancer resistance protein (BCRP). Uptake and efflux of 14 C-BT and 3 H-folic acid were measured in Caco-2, IEC-6, and MDA-MB-231 cell lines. mRNA expression of BCRP was detected by RT-PCR. Cell viability, proliferation, and differentiation were quantified with the lactate dehydrogenase, sulforhodamine B, and alkaline phosphatase activity assays, respectively. In both IEC-6 cells and Caco-2 cells, no evidence was found for the involvement of either MDR1 or MRPs in 14 C-BT efflux from the cells. In contrast, several lines of evidence support the conclusion that BT is a substrate of both rat and human BCRP. Indeed, BCRP inhibitors reduced 14 C-BT efflux in IEC-6 cells, both BT and BCRP inhibitors significantly decreased the efflux of the known BCRP substrate 3 H-folic acid in IEC-6 cells, and BCRP inhibitors reduced 14 C-BT efflux in the BCRP-expressing MDA-MB-231 cell line. In IEC-6 cells, combination of BT with a BCRP inhibitor significantly potentiated the effect of BT on cell proliferation. The results of this study, showing for the first time that BT is a BCRP substrate, are very important in the context of the high levels of BCRP expression in the human colon and the anticarcinogenic and anti-inflammatory role of BT at that level. So, interaction of BT with BCRP and with other BCRP substrates/inhibitors is clearly of major importance. butyrate efflux; colorectal cancer; IEC-6 cells; anticarcinogenic effect COLORECTAL CANCER (CRC) is a leading cause of cancer death in occidental countries (36). Butyrate (BT), a product of intestinal flora fermentation of dietary fiber, has a protective role in the prevention and progression of colorectal carcinogenesis (57). Indeed, this short-chain fatty acid plays a key role in colonic epithelium homeostasis, by having multiple important roles at that level: 1) it is the main energy source for colonocytes, 2) it promotes growth and proliferation of normal colonic epithelial cells, 3) it inhibits colon carcinogenesis (by suppressing growth of cancer cells, inducing differentiation and apoptosis and inhibiting cell proliferation), 4) it inhibits colon inflammation and oxidative stress, 5) it improves the colonic defence barrier function, and 6) it stimulates fluid and electrolyte absorption (reviews in Refs. 31, 68). 1The mechanism by which BT inhibits colon carcinogenesis seems to involve various effects on gene expression, which are mainly attributed to its capacity to act as a histone deacetylase inhibitor (HDAC), leading to hyperacetylation of histones and to incr...

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Effect of sodium butyrate on doxorubicin resistance and expression of multidrug resistance genes in thyroid carcinoma cells

Cited by 18 publications

References 22 publications

Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176)

Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176)

Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells

The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein

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