Histone deacetylase 1: a target of 9-hydroxystearic acid in the inhibition of cell growth in human colon cancer

Calonghi, Natalia; Cappadone, Concettina; Pagnotta, Eleonora; Boga, Carla; Bertucci, Carlo; Fiori, Jessica; Tasco, Gianluca; Casadio, Rita; Masotti, Lanfranco

doi:10.1194/jlr.m400424-jlr200

Cited by 42 publications

(59 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are three general classes of HDACs: class I HDACs, which are strictly nuclear, class II HDACs, which shuttle between the nucleus and cytoplasm, and class III HDACs, which require NADþ [23]. The class I HDACs 1, 2, and 3 have been reported to be upregulated in cancer cells from different tissue origins [24][25][26][27][28][29][30][31][32]. A recent metaanalysis of a variety of human cancers indicated that HDAC3 may be one of the most frequently upregulated genes in cancer cells [33].…”

Section: Introductionmentioning

confidence: 99%

HDAC3 overexpression and colon cancer cell proliferation and differentiation

Spurling

Godman

Noonan

et al. 2007

Molecular Carcinogenesis

109

View full text Add to dashboard Cite

An immunohistochemical analysis of human colorectal adenocarcinomas showed that cancer cells express widely varying levels of HDAC3. The SW480 colon cancer cell line was found to express high levels of HDAC3 compared to other colon cancer cell lines. p21 was poorly induced in SW480 cells relative to the lower HDAC3-expressing HT-29 cells. RNAi-induced reduction of HDAC3 in SW480 cells increased their constitutive, butyrate-, TSA-, and TNF-alpha-induced expression of p21, but did not cause all the gene expression changes induced upon general histone deacetylase (HDAC) inhibition. SW480 cells with lower HDAC3 expression appeared to be poised for gene expression responses with increased histone H4-K12 acetylation, but not K5, K8, or K16 acetylation. Even though p21 was readily activated in HT29 cells, HDAC3 siRNA nonetheless stimulated p21 expression in these cells to a greater degree than HDAC1 and HDAC2 siRNA. SW480 cells with lower HDAC3 levels displayed an enhanced cell cycle arrest and growth inhibition by butyrate, but without changes in apoptosis or sensitivity to chemotherapeutic agents. As reported for other colon cancer cell lines, butyrate induced the rapid downregulation of the secretory cell differentiation markers mucin 2 and intestinal trefoil factor in SW480 cells. Interestingly, selective HDAC3 inhibition was sufficient to downregulate these genes. Our data support a central role for HDAC3 in regulating the cell proliferation and differentiation of colon cancer cells and suggest a potential mechanism by which colon cancers may become resistant to luminal butyrate.

show abstract

Section: Introductionmentioning

confidence: 99%

HDAC3 overexpression and colon cancer cell proliferation and differentiation

Spurling

Godman

Noonan

et al. 2007

Molecular Carcinogenesis

109

View full text Add to dashboard Cite

show abstract

“…9 -HSA supplemented in micro-molar amounts to the human colon cancer cell line HT29 was previously shown to result in a strong inhibition of cell proliferation as well as cellular differentiation toward benign phenotype (Calonghi et al , 2005). To evaluate the effect of 9 -HSA on the proliferation of RPCs during retinogenesis and later on the stem cell niche of the retina, we assessed the proliferative state of retinae from embryos injected with 9 -HSA.…”

Section: Resultsmentioning

confidence: 99%

“…We previously demonstrated that tumor growth inhibitory effect of 9 -HSA on human colon carcinoma cells (HT29) in vitro was mediated through a direct fatty acid interaction, leading to a decrease of the enzymatic activity of the histone deacetylase 1 (HDAC1) (Calonghi et al , 2005; Parolin et al , 2012). In zebrafish HDAC1 was shown to be required for aspects of the eye and central nervous system development, and for the establishment of neural crest cell populations (Cunliffe, 2004; Cunliffe & Casaccia-Bonnefil, 2006; Harrison et al , 2011; Ignatius et al , 2013; Stadler et al , 2005; Yamaguchi, 2005).…”

Section: Resultsmentioning

confidence: 99%

“…To unravel the role of ROS scavenging and lipid peroxidation in RPCs, we investigated the in vivo function of 9 -HSA, a known downstream product of lipid peroxidation that we previously demonstrated as a regulator of cellular growth in different human tumor cell lines (Bertucci et al , 2002; Calonghi et al , 2007; Cavalli et al , 1991; Gesmundo et al , 1994). In these studies, we revealed by biochemical and structural modeling studies that, in vitro , 9 -HSA inhibits histone deacetylase 1 (HDAC1) activity by directly binding to its catalytic site (Calonghi et al , 2005; Parolin et al , 2012). Both 9 -HSA enantiomeric forms (R ) and (S)- 9 -HSA have the ability to inhibit HDAC1 activity, with ( R ) being more active, through a direct ligand-enzyme interaction, thereby blocking substrate access (Calonghi et al , 2005).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

Albadri

Naso

Gauron

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

21Reactive oxygen species (ROS) and downstream products of lipid oxidation are emerging as important 22 secondary messengers in tissue homeostasis. However their regulation and mechanism of action remain 23 poorly studied in vivo during normal development. Here we reveal that the fine regulation of hydrogen 24 peroxide (H2O2) levels at the degradation step by its scavenger Catalase is crucial to mediate the switch 25 from proliferation to differentiation in retinal progenitor cells (RPCs). We further show that altering the 26 levels of downstream products of the Redox signaling can also affect this switch. Indeed, we identify 9-27 hydroxystearic acid (9-HSA), an endogenous downstream lipid peroxidation product, as a mediator of 28 this effect in the zebrafish retina. In fact, RPCs exposed to higher amounts of 9-HSA failed to 29 differentiate and remained proliferative. We found that 9-HSA exerts its biological function in vivo by 30 inhibiting the activity of histone deacetylase 1. We finally show that the local and temporal 31 manipulation of H2O2 levels by catalase overexpression in RPCs was sufficient to trigger their premature 32 differentiation. Therefore the amount of H2O2 in RPCs is instructive of their ability to switch from 33 proliferation to differentiation. We propose a mechanism that acts in RPC and linking H2O2 homeostasis 34 and neuronal differentiation via the modulation of lipid peroxidation. 35 36 37 38 39 40 41 42 43 44 45 46 Key words 47 48 Redox signaling, lipid peroxidation, retinal progenitor cells, stem cell metabolism, neuronal 49 differentiation, H2O2, 9-HSA, HDAC1, zebrafish 50 4 retinogenesis, retinal progenitor cells (RPCs) start differentiating in a central to peripheral manner. By 3 81 dpf, the central retina is fully differentiated and a peripheral stem cell niche, known as the ciliary 82 marginal zone (CMZ), forms to ensure tissue homeostasis throughout the lifelong growth of the fish. The 83 CMZ comprises three main cell domains labeled by the expression of different transcription factors: the 84 rx2 domain, which contains RSCs (retinal stem cells) and RPCs, the ccnd1 (zebrafish equivalent to 85 cyclinD1) domain where cycling progenitors are found and an ath5 domain, which contains cycling and 86 committed RPCs (Agathocleous & Harris, 2009; Ohnuma & Harris, 2003; Reinhardt et al, 2015; Wan et 87 al, 2016). Due to this precise spatial and temporal organization, the zebrafish retina provides an excellent 88 model to assess the effects of ROS and lipid peroxidation downstream products on a stem cell and 89 progenitor cell population in vivo. Here we show that H2O2 levels are dynamically regulated in the 90 developing and in the mature neuro-retina where the expression of the H2O2 scavenger catalase follows a 91 pattern reminiscent of the neurogenic progression. H2O2 levels are further reflected on the lipid 92 peroxidation state in these cells as shown by the enrichment in the end marker of lipid peroxidation 4-93 hydroxynonenal (4-HNE) within the CMZ. Thus, H2O2 and lipid peroxidat...

show abstract

“…HDAC1 target genes include Bax, p21 WAF1/CIP1 , p27 KIP1 , and cytokeratin 18 (CK18) (Zhou et al, 2000; Lagger et al, 2002; Bandyopadhyay et al, 2004). While others have shown that HDAC1 may be inhibited by synthetic compounds [e.g., SAHA (Richon et al, 1998) and M344 (Kim et al, 2003)] or metabolic by‐products [e.g., 9‐HSA (Calonghi et al, 2005)] that have similar structures as the HDAC reaction transition‐state intermediate, it is reasonable to speculate that HDAC1 needs to be tightly regulated by a proactive mechanism in a cell type‐specific manner. To our knowledge, maspin is the first endogenous polypeptide inhibitor of HDAC1 identified.…”

Section: The Novel Co‐factors and Targets Of Maspinmentioning

confidence: 99%

A role of novel serpin maspin in tumor progression: The divergence revealed through efforts to converge

Shen

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

Maspin, a 42 kDa protein, belongs to the serine protease inhibitor (serpin) superfamily and is more closely related to the ovalbumin-like serpin subfamily (ov-serpins). More than a decade after the discovery of the maspin gene, our pursuit of the molecular mechanisms of maspin revealed a significant divergence of maspin from other serpins. This review article summarizes recent advances in the identification of maspin-binding proteins and the potential underlying molecular mechanisms of maspin in tumor progression. Specifically, the molecular interactions of maspin with the cell surface-associated pro-urokinase-type plasminogen activator (pro-uPA) and intracellular histone deacetylase 1 (HDAC1) are highlighted. Our new evidence suggests a new paradigm that maspin acts as a serpin-like molecule to inhibit serine protease-like targets. From an evolution point of view, the uniquely important function of maspin in development and tumor progression is likely due to its ancestral sequence code, and accordingly, its novel "meta"-serpin structure. It is reasonable to hypothesize that the conservation of a serine protease-like catalytic center in many molecules requires the co-existence of endogenous antagonists. The unique inhibitory interaction of maspin with both HDAC1 and pro-uPA might not be substituted by other serpins that have evolved to acquire higher target specificities. Thus, tumor suppressive maspin offers a unique therapeutic opportunity.

show abstract

Histone deacetylase 1: a target of 9-hydroxystearic acid in the inhibition of cell growth in human colon cancer

Cited by 42 publications

References 22 publications

HDAC3 overexpression and colon cancer cell proliferation and differentiation

HDAC3 overexpression and colon cancer cell proliferation and differentiation

Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

A role of novel serpin maspin in tumor progression: The divergence revealed through efforts to converge

Contact Info

Product

Resources

About