Differentiation and upregulation of heat shock protein 70 induced by a subset of histone deacetylase inhibitors in mouse and human embryonic stem cells

Park, Jeong-A; Kim, Young Eun; Seok, Hyun-Jeong; Park, Woo-Youn; Kwon, Hyung‐Joo; Lee, Younghee

doi:10.5483/bmbrep.2011.44.3.176

Cited by 17 publications

(12 citation statements)

References 28 publications

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“…We further showed that MS-275 initially caused an increase followed by a decrease of proliferation reminiscent of maturation processes. That in this setting MS-275 behaved similarly to SAHA (Vorinostat) is a point of particular interest given that i) Vorinostat has been reported to alter ESC pluripotency (Park et al, 2011) and ii) only class I HDACs (and mainly HDAC1 and 2) are inhibited by MS-275, thus restricting the epi-targets potentially responsible for this effect. Moreover, the concentration dependent dual growth effect – positive and negative proliferative action displayed by some epidrugs amongst which MS-275 – correlates the growth modulation with the enzyme inhibition suggesting target specificity.…”

Section: Discussionmentioning

confidence: 92%

The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells

et al. 2013

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SummaryExploitation of embryonic stem cells (ESC) for therapeutic use and biomedical applications is severely hampered by the risk of teratocarcinoma formation. Here, we performed a screen of selected epi-modulating compounds and demonstrate that a transient exposure of mouse ESC to MS-275 (Entinostat), a class I histone deacetylase inhibitor (HDAC), modulates differentiation and prevents teratocarcinoma formation. Morphological and molecular data indicate that MS-275-primed ESCs are committed towards neural differentiation, which is supported by transcriptome analyses. Interestingly, in vitro withdrawal of MS-275 reverses the primed cells to the pluripotent state. In vivo, MS275-primed ES cells injected into recipient mice give only rise to benign teratomas but not teratocarcinomas with prevalence of neural-derived structures. In agreement, MS-275-primed ESC are unable to colonize blastocysts. These findings provide evidence that a transient alteration of acetylation alters the ESC fate.

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Section: Discussionmentioning

confidence: 92%

The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells

et al. 2013

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“…Indeed, 5-aza-20-deoxycytidine, a potent demethylating agent, is also an autophagy promoter. 28 Differentiation inducing agents and inhibitors of histone deacetylase, such as valproic acid, 29 are potent inducers of autophagy in glioma cells, inducing autophagic cell death but not apoptosis. 30 Whether such agents can target radiation/Temozolomide resistant glioma stem cells is another hypothesis to test.…”

Section: Discussionmentioning

confidence: 99%

Autophagy and lysosomal related protein expression patterns in human glioblastoma

Giatromanolaki

Sivridis

Mitrakas

et al. 2014

Cancer Biology & Therapy

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Glioblastoma cells are resistant to apoptotic stimuli with autophagic death prevailing under cytotoxic stress. Autophagy interfering agents may represent a new strategy to test in combination with chemo-radiation. We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series of patients treated with post-operative radiotherapy. Experiments with glioblastoma cell lines (T98 and U87) were also performed to assess autophagic response under conditions simulating the adverse intratumoral environment. Glioblastomas showed cytoplasmic overexpression of autophagic proteins in a varying extent, so that cases could be grouped into low and high expression groups. 10/23, 5/23, 13/23, 5/23, 8/23 and 9/23 cases examined showed extensive expression of LC3A, LC3B, Beclin 1, Ulk 1, Ulk 2 and p62, respectively. Lysosomal markers Cathepsin D and LAMP2a, as well as the lyososomal biogenesis transcription factor TFEB were frequently overexpressed in glioblastomas (10/23, 11/23, and 10/23 cases, respectively). TFEB was directly linked with PTEN, Cathepsin D, HIF1α, LC3B, Beclin 1 and p62 expression. PTEN was also significantly related with LC3B but not LC3A expression, in both immunohistochemistry and gene expression analysis. Confocal microscopy in T98 and U87 cell lines showed distinct identity of LC3A and LC3B autophagosomes. The previously reported stone-like structure (SLS) pattern of LC3 expression was related with prognosis. SLS were inducible in glioblastoma cell lines under exposure to acidic conditions and 2DG mediated glucose antagonism. The present study provides the basis for autophagic characterization of human glioblastoma for further translational studies and targeted therapy trials.

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“…Upregulation of Hsp70 was also observed in hESC induced to differentiation by histone deacetylase inhibitors. 21 hESC and differentiated derivates were slightly different in Hsc70 (constitutive isoform) expression: it was a little higher in hESC. Moreover, we detected Hsc70 on the surface of ESC but not on their differentiated progeny.…”

Section: Cellsmentioning

confidence: 91%

Heat shock induces apoptosis in human embryonic stem cells but a premature senescence phenotype in their differentiated progeny

Алексеенко

Zemelko²,

Зенин³

et al. 2012

Cell Cycle

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Differentiation and upregulation of heat shock protein 70 induced by a subset of histone deacetylase inhibitors in mouse and human embryonic stem cells

Cited by 17 publications

References 28 publications

The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells

The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells

Autophagy and lysosomal related protein expression patterns in human glioblastoma

Heat shock induces apoptosis in human embryonic stem cells but a premature senescence phenotype in their differentiated progeny

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