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Vorinostat inhibits TP53. 24 / 25
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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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"Altogether, it seemed that vorinostat repressed HIF1 and TP53 in DU 145, but had less effect in PC-3 and 22Rv1."
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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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"Additionally, vorinostat induces p53 degradation by reducing its stability via inhibition of HDAC6, a key regulator of Hsp90 119."
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"5 muM vorinostat reduced E6 and E7 activity resulting in an elevation of p53, probably being the cause for the inhibition of viral DNA amplification."
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"As shown in Supplementary Figure S1, both SAHA and SAHA/5-AZA enhanced HSP90 acetylation and this effect may be involved in the reduction of mutp53 induced by SAHA."
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"SAHA downregulates mutp53 but not wtp53."
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"Furthermore, SAHA preferentially induces cytotoxicity in mutp53-expressing cancer cells, which is synergistic with 17AAG, and depletion of mutp53 by SAHA sensitizes MDA-MB-231 and T47D cells to camptothecin [102]."
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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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"Taken together, these data imply that mechanistically SAHA causes mutp53 degradation by inducing functional reactivation of MDM2 and CHIP."
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"We conclude that autophagy can be a relevant pathway for mutp53 degradation induced by SAHA, but its contribution to mutp53 destabilization and the consequences on cell death are likely context dependent."
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"Vorinostat pre-treatment significantly attenuated p53 stabilization in the presence of epirubicin (XREF_FIG)."
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"P53 was markedly downregulated at the protein as well as mRNA level by VPA, NaB and TSA and to a lesser extent by SAHA, LBH589 and MS-275 ( Fig. 1 A and B)."
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"To test the above hypothesis that, like mutant p53, RUNX2 could contribute to SAHA resistance of p53 mutated pancreatic cancer cells, we sought to assess the possible impact of RUNX2 knockdown on SAHA mediated cell death and mutant p53 expression in MiaPaCa-2 cells."
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"LBH589 (100 nM) and SAHA (5 muM) depleted MDM2 and p53, and induced PTEN and acetyl H3 in all LPS lines."
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"Vorinostat restores miR-150 and inhibits migration independently of p53 status."
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"Additionally, vorinostat pre-treatment attenuated the stabilization of total p53 protein induced by epirubicin exposure."
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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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"The downregulation of mutp53 by SAHA or SAHA/5-AZA was counteracted by Bortezomib (Figure 3D), which suggests that this protein underwent proteasomal degradation after these treatments."
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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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"XREF_BIBR, XREF_BIBR Similarly, SAHA, a histone deacetylase inhibitor, stimulates degradation of mutp53 by inhibiting HDAC6, a key positive regulator of HSP90."
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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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"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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"15 described that HDAC inhibitor suberoylanilide hydroxamic acid, which shows limited clinical activity to solid tumors, reduces p53 activity in response to DNA damage."
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