Histone deacetylase inhibitors: Multifunctional anticancer agents

Liu, Tao; Kuljaca, Selena; Tee, Andrew E.; Marshall, Glenn M.

doi:10.1016/j.ctrv.2005.12.006

Cited by 205 publications

(168 citation statements)

References 75 publications

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“…In mammals, there are four classes of HDACs (class I, IIa, IIb, III and IV) categorized based on homology to yeast HDACs [23]. Acetylation homeostasis can be easily modulated by the ever-growing members of HDAC inhibitors (HDACIs) [21,24], which currently categorized into six structurally distinct groups: short-chain fatty acids, hydroxamates, cyclic tetrapeptides, benzamides, electrophilic ketone, and miscellaneous [23,25].…”

Section: Introductionmentioning

confidence: 99%

Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury

Daosukho

Chen

Noel

et al. 2007

Free Radical Biology and Medicine

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Cardiac injury is a major complication for oxidative stress-generating anticancer agents exemplified by Adriamycin (ADR). Recently, several histone deacetylase inhibitors (HDACIs) including phenylbutyrate (PBA) have shown promise in the treatment of cancer with little known toxicity to normal tissues. PBA has been shown to protect against oxidative stress in normal tissues. Here, we examined whether PBA might protect heart against ADR toxicity in a mouse model. The mice were i.p. injected with ADR (20 mg/kg). PBA (400 mg/kg/day) was i.p. injected one day before and daily after the ADR injection for two days. We found that PBA significantly decreased the ADR-associated elevation of serum lactase dehydrogenase (LDH) and creatine kinase (CK) activities, and diminished ADR-induced ultrastructual damages of cardiac tissue by more than 70%. Importantly, PBA completely rescued ADR-caused reduction of cardiac functions exemplified by ejection fraction and fraction shortening, and increased cardiac MnSOD protein and activity. Our results reveal a previously unrecognized role of HDACIs in protecting against ADR-induced cardiac injury, and suggest that PBA may exert its cardioprotective effect, in part, by the increase of MnSOD. Thus, combining HDACIs with ADR could add a new mechanism to fight cancer while simultaneously decrease ADR-induced cardiotoxicity.

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Section: Introductionmentioning

confidence: 99%

Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury

Daosukho

Chen

Noel

et al. 2007

Free Radical Biology and Medicine

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“…[14][15][16] HDACi play a crucial role in the control of cell cycle progression and programmed cell death, so that they are currently investigated as a potential new family of anticancer agents both in hematologic and solid cancers. 17 Several classes of HDACi have been identified, in particular the hydroxamate family, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), which inhibit class I and class II HDACs. 18 We recently described a new synthetic HDAC class I inhibitor (ITF2357), with a potent anti-proliferative and pro-apoptotic activity against cells from hepatocellular carcinoma, acute myelogenous leukemia (AML) and multiple myeloma (MM).…”

Section: Introductionmentioning

confidence: 99%

The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2V617F

et al. 2007

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We investigated the activity of ITF2357, a novel histone deacetylase inhibitor (HDACi) with antitumor activity, on cells carrying the JAK2 V617F mutation obtained from polycythemia vera (PV) and essential thrombocythemia (ET) patients as well as the HEL cell line. The clonogenic activity of JAK2 V617F mutated cells was inhibited by low concentrations of ITF2357 (IC 50 0.001-0.01 lM), 100-to 250-fold lower than required to inhibit growth of normal or tumor cells lacking this mutation. Under these conditions, ITF2357 allowed a seven fold increase in the outgrowth of unmutated over mutated colonies. By western blotting we showed that in HEL cells, ITF2357 led to the disappearance of total and phosphorylated JAK2 V617F as well as pSTAT5 and pSTAT3, but it did not affect the wild-type JAK2 or STAT proteins in the control K562 cell line. By real-time PCR, we showed that, upon exposure to ITF2357, JAK2 V617F mRNA was not modified in granulocytes from PV patients while the expression of the PRV-1 gene, a known target of JAK2, was rapidly downmodulated. Altogether, the data presented suggest that ITF2357 inhibits proliferation of cells bearing the JAK2 V617F mutation through a specific downmodulation of the JAK2 V617F protein and inhibition of its downstream signaling.

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“…HDAC inhibitors may induce cell cycle arrest, differentiation, and apoptosis in cancer cells. Thus, HDAC inhibitors are considered promising tools in the prevention and treatment of the disease (Liu et al 2006), and synthetic inhibitors such as belinostat are already being tested in clinical trials (Ma et al 2010). Importantly, HDAC activity may be modulated by a number of dietary compounds.…”

Section: Acetylation Of Histonesmentioning

confidence: 99%

Nutrition, Histone Epigenetic Marks, and Disease

Zempleni

Liu

Xue

2013

Environmental Epigenomics in Health and Disease

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The dietary intake of essential nutrients and bioactive food compounds is a process that occurs on a daily basis for the entire life span. Therefore, your diet has a great potential to cause changes in the epigenome. Known histone modifications include acetylation, methylation, biotinylation, poly(ADP-ribosylation), ubiquitination, and sumoylation. Some of these modifications depend directly on dietary nutrients. For other modifications, bioactive dietary compounds may alter the activities of enzymes that establish or remove histone marks, thereby altering the epigenome. This chapter provides an overview of diet-dependent epigenomic marks in histones and their links with human health.

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Histone deacetylase inhibitors: Multifunctional anticancer agents

Cited by 205 publications

References 75 publications

Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury

Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury

The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2V617F

Nutrition, Histone Epigenetic Marks, and Disease

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