The Synthesis of N-Hydroxy-N'-phenyloctanediamide and Its Inhibitory Effect on Proliferation of AXC Rat Prostate Cancer Cells

Stowell, John C.; Huot, Rachel I.; Voast, L Van

doi:10.1021/jm00008a020

Cited by 54 publications

(40 citation statements)

References 3 publications

(7 reference statements)

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“…Compounds and reagents SAHA was synthesised as described previously [13], dissolved in dimethyl sulfoxide to 50 mM and stored at -80uC. All reagents were from Sigma Aldrich (St. Louis, MI, USA) unless stated otherwise.…”

Section: Methodsmentioning

confidence: 99%

Suberoylanilide hydroxamic acid: a potential epigenetic therapeutic agent for lung fibrosis?

Wang¹,

C²,

Finger³

et al. 2009

European Respiratory Journal

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Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential.Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-b1 with or without SAHA. Collagen deposition, a-smooth muscle actin (a-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations.SAHA abrogated TGF-b1 effects on all the fibroblast lines by preventing their transdifferentiation into a-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of a-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations.Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis.

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Section: Methodsmentioning

confidence: 99%

Suberoylanilide hydroxamic acid: a potential epigenetic therapeutic agent for lung fibrosis?

Wang¹,

C²,

Finger³

et al. 2009

European Respiratory Journal

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“…MS-275 (Calbiochem, Bad Soden/Ts., Germany) is a benzamide, suberoylanilide hydroxamic acid (SAHA) (synthesized according to 16 ), Trichostatin A (TSA) (Sigma, Taufkirchen, Germany); and compounds from our lab (see below) are hydroxamic acids, and VPA is a short chain fatty acid. M344, M360, D85, SW55 and SW187 are new drugs that were developed and synthesized by one of us (M.J.).…”

Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

Inhibitors of histone deacetylases as potential therapeutic tools for high‐risk embryonal tumors of the nervous system of childhood

Furchert

Lanvers-Kaminsky

Juürgens

et al. 2007

Intl Journal of Cancer

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The origin of malignant embryonal tumors is incompletely understood and certain risk groups remain difficult to treat. The epigenetic structure of DNA and its lesions play a role in the origin of these neoplasms. Manipulation of the epigenome may offer novel treatment options. The authors evaluated the cytotoxicity of histone deacetylase inhibitors (HDI) [MS-275, SAHA, TSA, M344, M360, D85, SW55, SW187 and valproic acid (VPA)] on 13 embryonal tumor cell lines [4 medulloblastomas, 5 neuroblastomas, 2 atypical teratoid/rhabdoid tumors (AT/RT), and 2 malignant rhabdoid tumors of the kidney (RTK)] in MTT assay. In addition, HDI effects on hyperacetylation, reexpression of growth regulatory genes and apoptosis were characterized by Western analysis, RT-PCR and annexin-V staining. All HDI inhibited cell proliferation in a time-and dose-dependent manner. VPA was least cytotoxic with GI 50 values after 72 hr ranging from 53.6 to 332.9 lM, while TSA was most efficient with GI 50 values after 72 hr ranging from 0.01 to 8.8 lM. M344 and M360 were also highly effective. Western blot revealed hyperacetylation of histone H4 after HDI treatment. Reactivation of several genes including the proapoptotic CASP8 was identified by RT-PCR. Annexin-V staining demonstrated a dose and time dependent induction of apoptosis. HDI inhibited the growth of medulloblastoma, neuroblastoma and rhabdoid tumors in vitro. Treatment with HDI induced the reactivation of growth regulatory genes and consequently apoptosis. Our results warrant further studies and may help in the design of new protocols geared at the treatment of high risk embryonal tumors. ' 2007 Wiley-Liss, Inc.

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“…46), the fluorinated derivative of the clinically relevant HDACI SAHA, was also determined using the WST-1 assay as described above. Cells were treated with 2, 5, and 10 Amol/L FSAHA either in the presence of 1 mmol/L BLT or in the presence of DMSO (in which BLT had to be dissolved first due to its low solubility in growth medium).…”

Section: Mrs Studies Of Blt Cleavagementioning

confidence: 99%

Detection of histone deacetylase inhibition by noninvasive magnetic resonance spectroscopy

Sankaranarayanapillai¹,

Tong²,

Maxwell³

et al. 2006

Molecular Cancer Therapeutics

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Histone deacetylase (HDAC) inhibitors are new and promising antineoplastic agents. Current methods for monitoring early response rely on invasive biopsies or indirect blood-derived markers. Our goal was to develop a magnetic resonance spectroscopy (MRS) -based method to detect HDAC inhibition. The fluorinated lysine derivative Boc-Lys-(Tfa)-OH (BLT) was investigated as a 19 F MRS molecular marker of HDAC activity together with 31 P MRS of endogenous metabolites. In silico modeling of the BLT-HDAC interaction and in vitro MRS studies of BLT cleavage by HDAC confirmed BLT as a HDAC substrate. BLT did not affect cell viability or HDAC activity in PC3 prostate cancer cells. PC3 cells were treated, in the presence of BLT, with the HDAC inhibitor p-fluorosuberoylanilide hydroxamic acid (FSAHA) over the range of 0 to 10 Mmol/L, and HDAC activity and MRS spectra were monitored. Following FSAHA treatment, HDAC activity dropped, reaching 53% of control at 10 Mmol/L FSAHA. In parallel, a steady increase in intracellular BLT from 14 to 32 fmol/cell was observed. BLT levels negatively correlated with HDAC activity consistent with higher levels of uncleaved BLT in cells with inhibited HDAC. Phosphocholine, detected by 31

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The Synthesis of N-Hydroxy-N'-phenyloctanediamide and Its Inhibitory Effect on Proliferation of AXC Rat Prostate Cancer Cells

Cited by 54 publications

References 3 publications

Suberoylanilide hydroxamic acid: a potential epigenetic therapeutic agent for lung fibrosis?

Suberoylanilide hydroxamic acid: a potential epigenetic therapeutic agent for lung fibrosis?

Inhibitors of histone deacetylases as potential therapeutic tools for high‐risk embryonal tumors of the nervous system of childhood

Detection of histone deacetylase inhibition by noninvasive magnetic resonance spectroscopy

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