IndraLab

Statements

Vorinostat inhibits TP53. 10 / 20
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"We found that SAHA or NaB, alone or in combination with camptothecin (CPT) treatment, inhibited accumulation of wild-type p53 protein in HCT116 cells (XREF_FIG)."
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"In addition, HIF1A and TP53 protein were downregulated by vorinostat under normoxia and hypoxia in DU 145, but not in the others (XREF_FIG)."
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"This is due to degradation of mutp53 by SAHA, which is likely caused by hyperacetylation and inhibition of HSP90 through inactivation of HDAC6 by SAHA [XREF_BIBR]."
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"SAHA downregulates mutp53 but not wtp53."
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"In the human cancer lines MDA-MB-231 (mutp53-R280K) and DLD1 (mutp53-S241F), SAHA induced a significant mutp53 degradation."
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"Additionally, vorinostat pre-treatment attenuated the stabilization of total p53 protein induced by epirubicin exposure."
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"Vorinostat restores miR-150 and inhibits migration independently of p53 status."
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"Interestingly, the silencing of HDAC10 (XREF_SUPPLEMENTARY) resulted in the most efficient reduction of p53 (XREF_FIG), exhibiting a 25% decrease in protein expression, suggesting that the observed SAHA mediated reduction of HIF-1alpha and p53 is occurring through inhibition of different HDAC family members."
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"However, SAHA-mediated ALV replication enhancement is ;3-fold in cells' depletion of p53, consistent with the above results that p53 recruited HDAC1/ 2 in ALV LTR (Fig. 4C) ."
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"Moreover , Suberoylanilide hydroxamic acid ( SAHA ) activates tumor suppressor p53 and Rb1 through phosphorylation and causes apoptosis in nasopharyngeal carcinoma ( NPC ) cells ( Huang et al ) ."
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Vorinostat inhibits mutated TP53. 9 / 9
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"Vorinostat sensitized DU145 cells to PARPi/IR and decreased mutant p53."
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"Wang et al. described that SAHA causes a massive reduction of mutant p53 through the disruption of the physical interaction between YY1 and HDAC8 [XREF_BIBR]."
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"Specifically, suberoylanilide hydroxamic acid (SAHA, also known as vorinostat), a FDA approved HDACi that inhibits class I, II, and IV HDACs, induces degradation of mutant p53 by inhibiting HDAC6 activity, an essential positive regulator of Hsp90, and subsequent disruption of the HDAC6/Hsp90/mutant p53 complex, leading to mutant p53 ubiquitination by MDM2 and CHIP."
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"Vorinostat did not completely inhibit the mutant p53 population, and this was reflected in the estimated inhibitory coefficient for mutant p53 (I mp53 = 0.202 muM -1; Table 1)."
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"Importantly, we could demonstrate for the first time that the HDAC inhibitor SAHA is able to effectively and specifically downregulate mutant p53 protein by promoting its degradation, while having no effect on wild-type p53 protein levels (XREF_FIG)."
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"We found that mutant p53 protein was markedly decreased by ATO, 17AAG, or SAHA, and further decreased by combination of ATO with 17AAG or SAHA (XREF_FIG)."
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"To further explore whether inhibitors of HSP90 and HDACs are capable of inducing Pirh2 expression to degrade mutant p53, HaCaT and MIA PaCa-2 cells were treated with 17AAG or SAHA."
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"cl.PARP.BCL-xL; BcL-xL (0) = 1 Vorinostat stimulates wild type p53 (wtp53) and inhibits mutant p53 (mp53) expression.10, 19, 20 In this study, p53 initially decreased, began to return to baseline around 24 hours, and eventually increased beyond the baseline."
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"It is known that SAHA induces the degradation of mutant p53 protein via inhibiting HDAC6, a member of class IIb HDACs."
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Vorinostat inhibits TP53-R270H. 2 / 2
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"For the inhibition of p53 R270H, organoids were treated with pan-histone deacetylase inhibitor suberoylanilide hydroxamic acid (Sigma)."
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"28 We confirmed that SAHA treatment abolished the nuclear accumulation of p53 R270H in Apc Delta716 Trp53 R270H and R270H organoids in a dose dependent manner (XREF_FIG)."
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