Mechanism and stereoselectivity of HDAC I inhibition by (R)-9-hydroxystearic acid in colon cancer

Parolin, Carola; Calonghi, Natalia; Presta, Enrica; Boga, Carla; Caruana, Paolo; Naldi, Marina; Andrisano, Vincenza; Masotti, Lanfranco; Sartor, Giorgio

doi:10.1016/j.bbalip.2012.07.007

Cited by 32 publications

(42 citation statements)

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“…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%

“…Racemic 9 -HSA was prepared as previously reported (Calonghi et al , 2005), as well as 10-HSA (Ebert et al , 2012). Pure ( R )- 9 -HSA was prepared from Dimorphotheca sinuata seeds according to the procedure previously described (Parolin et al , 2012; Boanini et al , 2016) and its optical purity (>99%) was determined by H NMR analysis after derivatization with ( R )-(-)-O-acetylmandelic acid (Parolin et al , 2012). The synthesized ( R )- 9 -HSA enantiomere, previously shown to be more efficient in inhibiting HDAC1 activity was used for exogenous administration (Parolin et al , 2012).…”

Section: Methodsmentioning

confidence: 99%

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Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

Albadri

Naso

Gauron

et al. 2019

Preprint

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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...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

Albadri

Naso

Gauron

et al. 2019

Preprint

Self Cite

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show abstract

“…Some fatty acids attenuate growth and induce apoptosis in a variety of human cancer cell lines [3][4][5]8,9,13,14,[16][17][18]. Fatty acid-induced apoptosis may be correlated with increased activity of caspases [4,7,16,17].…”

Section: Discussionmentioning

confidence: 96%

“…Palmitic acid treatment leads to induction of ER stress and apoptosis of pancreatic b-cells, hepatocytes, and cardiomyocytes [6][7][8]. (R)-9-Hydroxystearic acts as a histone deacetylase inhibitor, exerting antiproliferative effect in colon cancer [9]. However, little is known about the biological function of hydroxyl fatty acids acquired from bioconversion.…”

Section: Introductionmentioning

confidence: 99%

ω-Hydroxyundec-9-enoic acid induces apoptosis through ROS-mediated endoplasmic reticulum stress in non-small cell lung cancer cells

Yang

Kim

Park

2014

Biochemical and Biophysical Research Communications

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Fatty Acids as Novel Building‐Blocks for Biomaterial Synthesis

Kumar¹

2019

Soil Microenvironment for Bioremediation and Polymer Production

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Mechanism and stereoselectivity of HDAC I inhibition by (R)-9-hydroxystearic acid in colon cancer

Cited by 32 publications

References 37 publications

Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

Redox signalingvialipid peroxidation regulates retinal progenitor cell differentiation

ω-Hydroxyundec-9-enoic acid induces apoptosis through ROS-mediated endoplasmic reticulum stress in non-small cell lung cancer cells

Fatty Acids as Novel Building‐Blocks for Biomaterial Synthesis

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