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Cited by 69Histone Deacetylase Inhibitors ResearchEnzyme function and inhibitionSynthesis and biological activity

A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth

Open access
Kaliszczak, M, Trousil, S, Åberg, O, Perumal, M, Nguyen, Q-D, Aboagye, E O·2013·British Journal of Cancer
DOI 10.1038/bjc.2012.576PMC PMC3566806
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Abstract

BACKGROUND: This study investigates whether a histone deacetylase subtype 6 (HDAC6) inhibitor could be used in the treatment of solid tumours. METHODS: We evaluated the effect of a novel inhibitor, C1A, on HDAC6 biochemical activity and cell growth. We further examined potential of early noninvasive imaging of cell proliferation by [(18)F]fluorothymidine positron emission tomography ([(18)F]FLT-PET) to detect therapy response. RESULTS: C1A induced sustained acetylation of HDAC6 substrates, α-tubulin and HSP90, compared with current clinically approved HDAC inhibitor SAHA. C1A induced apoptosis and inhibited proliferation of a panel of human tumour cell lines from different origins in the low micromolar range. Systemic administration of the drug inhibited the growth of colon tumours in vivo by 78%. The drug showed restricted activity on gene expression with <0.065% of genes modulated during 24 h of treatment. C1A treatment reduced tumour [(18)F]FLT uptake by 1.7-fold at 48 h, suggesting that molecular imaging could provide value in future studies of this compound. CONCLUSION: C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets leading to growth inhibition of a diverse set of cancer cell lines. This property together with the favourable pharmacokinetics and efficacy in vivo makes it a candidate for further pre-clinical and clinical development.

AI snapshot

Written from the paper’s full text.

TL;DR

C1A is a novel hydroxamate HDAC inhibitor that preferentially inhibits HDAC6 over HDAC1 and shows antiproliferative/apoptotic activity across diverse cancer cell lines and in a colon xenograft model. It has favourable pharmacokinetics, inhibits tumour growth by up to 78%, and reduces tumour [18F]FLT uptake, supporting further preclinical/clinical development.

Key findings

  • C1A inhibited HDAC6 with IC50=479 nℳ versus HDAC1 IC50=14 μℳ; HDAC8 was also inhibited at submicromolar concentrations. It increased acetylation of HDAC6 substrates α-tubulin and HSP90, with sustained α-tubulin acetylation 3 h after washout, unlike SAHA, and did not increase histone H3 acetylation.
  • Across 17 human cancer cell lines, C1A had a mean GI50 of 3.1±2.2 μℳ after 72 h; in HCT-116 cells, sub-G1 increased from 4% untreated to 64% at 10 μℳ, and caspase-3/7 activity increased.
  • In HCT-116 xenografts, C1A produced tumour growth inhibition of 57%, 69%, and 78% at 40 mg kg−1 q.o.d., 20 mg kg−1 q.d., and 20 mg kg−1 b.i.d., respectively, with no general toxicity by body weight.
  • C1A reduced tumour [18F]FLT uptake 1.7-fold at 48 h (NUV60 1.77±0.11 before treatment to 1.06±0.15 at 48 h; P=0.0001), and only 13 of 20,000 genes (0.065%) were deregulated at 24 h.

Methods

  • Preclinical in vitro and in vivo study using recombinant HDAC enzyme assays, molecular modelling, immunoblotting, cell-cycle flow cytometry, caspase-3/7 assays, and sulphorhodamine B growth inhibition assays in a panel of 17 human cancer cell lines.
  • In vivo work used HCT-116 colon cancer xenografts in female nu/nu-BALB/c athymic nude mice; C1A was given intraperitoneally, with PK profiling in female BALB/c mice.
  • Main analyses included tumour volume measurement, [18F]FLT-PET imaging, Ki-67 immunostaining, active caspase-3/TUNEL immunohistochemistry, and Affymetrix human genome U219 microarray gene expression profiling.

Limitations

  • The paper states that gene expression changes after C1A cannot be wholly attributed to HDAC6 because accumulation of C1A in tumour cells to levels high enough to inhibit other HDAC classes cannot be completely ruled out.
  • The paper states that further studies are required to elucidate the exact mechanism leading to apoptosis, to directly link inhibition of C1A targets to growth inhibition, and to confirm in a larger cell-line cohort whether HDAC6 expression predicts sensitivity.
  • Evident from the text: in vivo efficacy, imaging, and gene-array analyses were performed mainly in the HCT-116 xenograft model, and ACY-1215 could not be compared structurally because its chemical structure was not available.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/bjc.2012.576

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 27 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Following a single dose of C1A at 40 mg kg−1, acetylated α-tubulin was detectable at 6 h and sustained up to 24 h in HCT-116 tumours.

    “Following a single dose of C1A at 40 mg kg−1, acetylated α-tubulin could be detected at 6 h and sustained up to 24 h (Figure 5A).”
    Quote in the paperSubstantial claim
  • Findingown data

    C1A inhibited the growth of a panel of 17 human cancer cell lines, including cell lines derived from 8 different histological types of solid tumours and one type of B-cell malignancy, with a mean GI50 of 3.1±2.2 μM following 72 h continuous exposure.

    “C1A inhibited the growth of a panel of 17 human cancer cell lines, including cell lines derived from 8 different histological types of solid tumours and one type of B-cell malignancy, with a mean growth inhibitory effect (GI50) of 3.1±2.2 μℳ following 72 h continuous exposure (Table 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    p21 levels remained unchanged following treatment with C1A.

    “In contrast, p21 levels remained unchanged following treatment with C1A.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no general toxicity in any of the treated cohorts as determined by changes in body weight.

    “there was no general toxicity in any of the treated cohorts as determined by changes in body weight (Figure 4D).”
    Quote in the paperSubstantial claim
  • Findingown data

    Cells transfected with HDAC6 shRNA had an increased sub-G1 population, from 1.2% for shRNA-scramble to 31.8% for shRNA HDAC6.

    “Flow cytometry studies revealed that, cells transfected with HDAC6 shRNA had an increased sub-G1 population (from 1.2% for shRNA-scramble to 31.8% for shRNA HDAC6)”
    Quote in the paperSubstantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data

    In animals treated with C1A for 48 h, tumour [18F]FLT uptake decreased 1.7-fold compared with vehicle-treated mice; NUV60 was 1.77±0.11 before treatment, 1.59±0.10 (P=0.033) at 24 h, and 1.06±0.15 (P=0.0001) at 48 h.

    “There was a 1.7-fold decrease in tumour [18F]FLT uptake in animals treated with C1A for 48 h compared with vehicle-treated mice; NUV60 was 1.77±0.11 before treatment and decreased to 1.59±0.10 (P=0.033) at 24 h and 1.06±0.15 (P=0.0001) at 48 h after initiating treatment (Figure 5B).”
    • Also stated in: § Discussion · plain
      “C1A treatment reduced tumour [18F]FLT uptake by 1.7-fold at 48 h”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HCT-116 cells transfected with HDAC6 shRNA showed increased acetylation of α-tubulin concomitant with a decrease of CDK4.

    “Similarly, HCT-116 cells transfected with HDAC6 shRNA showed increased acetylation of α-tubulin concomitant with a decrease of CDK4 (Supplementary Figure S2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The growth inhibitory potency of C1A was not affected by DNA repair defects, in contrast to the DNA alkylating agent chlorambucil.

    “We showed that, in contrast to the DNA alkylating agent chlorambucil, the growth inhibitory potency of C1A was not affected by DNA repair defects (Figure 2F)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both C1A and SAHA were associated with a decline of CDK4 expression, consistent with HSP90 inhibition.

    “Both C1A and SAHA were associated with a decline of CDK4 expression, consistent with HSP90 inhibition (Figure 2E).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The pharmacokinetics of C1A followed a two-compartment model with an apparent terminal half-life of 10 h.

    “The PKs of C1A followed a two-compartment model with an apparent terminal half-life of 10 h (Figure 4A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After continuous 4 h treatment with 10 μM and subsequent washout, acetylation of α-tubulin was maintained for 3 h after washout of C1A but not with SAHA.

    “When treated continuously for 4 h (10 μℳ) and drug was subsequently removed by washing to mimic intermittent dosing in vivo, acetylation of α-tubulin was maintained for 3 h after washout of C1A but not with SAHA (Figure 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no relationship between the growth inhibitory effect of C1A and HDAC6 nor HDAC1 protein expression.

    “There was no relationship between the growth inhibitory effect of C1A and HDAC6 nor HDAC1 protein expression (Supplementary Figure S7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C1A treatment was associated with a tumour growth delay (TGD2x) of 4.0±0.8, 3.8±1.2 and 5.7±1.4 days and a tumour growth inhibition (TGI) of 57, 69 and 78% compared with vehicle at 40 mg kg−1 q.o.d., 20 mg kg−1 q.d. and 20 mg kg−1 b.i.d., respectively.

    “C1A treatment was associated with a tumour growth delay (TGD2x) of 4.0±0.8, 3.8±1.2 and 5.7±1.4 days and a tumour growth inhibition (TGI) of 57, 69 and 78% compared with vehicle at 40 mg kg−1 q.o.d., 20 mg kg−1 q.d. and 20 mg kg−1 b.i.d., respectively”
    • Also stated in: § Results: · plain
      “Systemic administration of the drug inhibited the growth of colon tumours in vivo by 78%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Ki-67 immunostaining decreased in C1A-treated tumours, consistent with the reduction in tumour [18F]FLT uptake.

    “Ki-67 immunostaining decreased in these tumours in keeping with the reduction in tumour [18F]FLT uptake (1.7-fold; P<0.0001) (Figure 5C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C1A exhibited linear pharmacokinetic characteristics with dose-proportional increases observed in plasma concentration.

    “C1A exhibited linear PK characteristics with dose-proportional increases observed in plasma concentration (Figure 4B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Caspase-3/7 activation by C1A occurred in the A2780 cell line but not in the caspase-3-deficient MCF7 breast cancer cell line.

    “Caspase-3/7 activation by C1A also occurred in A2780 cell line but not in the caspase-3-deficient MCF7 breast cancer cell line (Supplementary Figure S3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C1A inhibited class I/II HDACs, and sirtuins, with highest affinity for HDAC6 (IC50=479 nM) versus HDAC1 (IC50=14 μM).

    “C1A inhibited class I/II HDACs, and sirtuins, with highest affinity for HDAC6 (IC50=479 nℳ) versus HDAC1 (IC50=14 μℳ; Figure 1F and Supplementary Table S1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Proliferation of cells transfected with HDAC6 shRNA was inhibited by 24% after 3 days of seeding, but unlike drug treatment no difference in caspase-3/7 activity was detectable.

    “Proliferation of cells transfected with HDAC6 shRNA was inhibited by 24% after 3 days of seeding, but unlike drug treatment no difference in caspase-3/7 activity was detectable (Supplementary Figure S6).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Phenotypic effects of HDAC6 knockdown by shRNA overlapped with those of C1A treatment, including inhibition of proliferation, increase in sub-G1 fraction, increased acetylation of α-tubulin and decreased CDK4 expression, with unremarkable changes in acetylation of histone H3.

    “Phenotypic effects of HDAC6 knockdown by shRNA overlapped with those of C1A treatment, including inhibition of proliferation, increase in sub-G1 fraction, increased of acetylation of α-tubulin and decreased CDK4 expression with unremarkable changes in acetylation of histone H3”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HDAC6 expression did not predict sensitivity to C1A; HDAC6 was ubiquitously expressed with no significant differences across cell lines, and differences in growth sensitivity between cell lines were only ∼10-fold.

    “This did not appear to be the case as HDAC6 was ubiquitously expressed with no significant differences across cell lines. Furthermore, the differences in growth sensitivity between the cell lines were only ∼10-fold.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Molecular modelling analysis suggested favourable interaction between C1A and HDA6cdII relative to unfavourable binding of the aniline mustard of C1A to a solvent-exposed groove within HDAC1cd.

    “Molecular modelling analysis suggested favourable interaction between C1A and HDA6cdII relative to the unfavourable binding of the aniline mustard of C1A to a solvent-exposed groove within HDAC1cd.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C1A treatment induced a time-dependent increase in α-tubulin in tumours of mice, with no change in histone H3 in tumours.

    “Consistent with proposed mechanism of action, we observed a time-dependent induction of α-tubulin in tumours of mice treated with C1A, with no change in histone H3 in tumours.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Following C1A treatment, the following genes were upregulated: BST2, FHL1, NBPF(8-11, 14-16), XAF1, PIP5KL1, BAX, SRD5A1, DHCR24, TAPBP, PTPRG, IPO7 and RAD23B; HIST2H2AC was downregulated.

    “The following genes were upregulated: BST2, FHL1, NBPF(8-11, 14-16), XAF1, PIP5KL1, BAX, SRD5A1, DHCR24, TAPBP, PTPRG, IPO7 and RAD23B; HIST2H2AC was downregulated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C1A treatment increased apoptosis markers in HCT-116 tumours: activated caspase-3 expression increased 6-fold (P=0.0082), TUNEL staining increased 7-fold (P<0.0001), and DNA content decreased (P=0.023).

    “Activated caspase-3 expression and subsequent fragmented DNA staining (TUNEL) increased 6- (P=0.0082) and 7-fold (P<0.0001), respectively, together with a decrease of DNA content (P=0.023; Figure 5D).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    HDAC6 has recently emerged as an attractive target for the treatment of cancer.

    “HDAC6 has recently emerged as an attractive target for the treatment of cancer (Boyault et al, 2007; Lee et al, 2008; Kawada et al, 2009; Rivieccio et al, 2009).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Boyault et al, 2007 source

      Not checked in the free run.

    • cites Lee et al, 2008 source

      Not checked in the free run.

    • cites Kawada et al, 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets leading to growth inhibition of a diverse set of cancer cell lines.

    “C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets leading to growth inhibition of a diverse set of cancer cell lines.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The preferential activity of C1A on HDAC6 inhibited cell growth and induced cell death in a variety of cell lines.

    “These studies suggests that the preferential activity of C1A on HDAC6 inhibited cell growth and induced cell death in a variety of cell lines.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    HDAC6 has been described as predominantly cytoplasmic, but has also been suggested to act as a nuclear cofactor.

    “Although HDAC6 has been described as being predominantly cytoplasmic, it has also been suggested to act as a nuclear cofactor (Palijan et al, 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Palijan et al, 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    [18F]FLT-PET uptake was previously shown to be altered only at later time points with broad-spectrum HDACI LAQ-824.

    “[18F]FLT-PET uptake was previously shown to be altered only at later time points with broad-spectrum HDACI LAQ-824 (Leyton et al, 2006a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Leyton et al, 2006a

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ACY-1215 was reported as an inhibitor of multiple myeloma cell growth when combined with bortezomib.

    “More recently, a new HDAC6 inhibitor ACY-1215 was reported as an inhibitor of multiple myeloma cell growth when combined with bortezomib (Santo et al, 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Santo et al, 2012 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets, leading to growth inhibition of a diverse set of cancer cell lines.

    “In conclusion, C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets, leading to growth inhibition of a diverse set of cancer cell lines.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Acetylation of α-tubulin promotes microtubule stabilisation, may distort mitosis and trigger apoptosis, and can affect changes in cell motility and hence invasion and metastasis of cancer cells.

    “Acelylation of α-tubulin, which promotes microtubule stabilisation, may distort mitosis and trigger apoptosis (Matsuyama et al, 2002); it can also affect changes in cell motility and, hence, invasion and metastasis of cancer cells (Hubbert et al, 2002).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Matsuyama et al, 2002 source

      Not checked in the free run.

    • cites Hubbert et al, 2002 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    C1A, a potent small molecule inhibitor of HDAC, in particular HDAC6, inhibits proliferation and induces cell death in tumour cell lines from diverse histological backgrounds.

    “We have shown that a potent small molecule inhibitor of HDAC, in particular HDAC6, inhibits proliferation and induces cell death in tumour cells lines from diverse histological background.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Although HDAC6 modulation was seen in vivo, the changes in gene expression after C1A treatment cannot be wholly attributed to an HDAC6 mechanism because accumulation of C1A into tumour cells to levels high enough to also inhibit other HDAC classes cannot be completely ruled out.

    “Notably, however, although HDAC6 modulation was seen in vivo, we cannot wholly attribute the changes in gene expression seen after C1A treatment to an HDAC6 mechanism, as we cannot completely rule out accumulation of C1A into the tumour cells to levels high enough to also inhibit other HDAC classes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The mustard moiety in C1A does not induce non-specific DNA alkylation and is unlikely to significantly contribute to a DNA alkylation-dependent cell death.

    “These studies (Figure 2F) suggested that the mustard moiety in C1A does not induce non-specific DNA alkylation and, thus, unlikely to significantly contribute to a DNA alkylation-dependent cell death.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The HCT-116 xenograft model was chosen because it represented the highest HDAC6 expression, has intermediate sensitivity to C1A, and has been used extensively as a model for other HDACIs.

    “HCT-116 xenograft model was chosen because it represented the highest HDAC6 expression, has intermediate sensitivity to C1A (thus, data are not biased to high sensitivity tumours only) and it has been used extensively as a model for other HDACIs, including genomic and imaging studies (Leyton et al, 2006a; Witter et al, 2008; LaBonte et al, 2009).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Leyton et al, 2006a

      Not checked in the free run.

    • cites Witter et al, 2008 source

      Not checked in the free run.

    • cites LaBonte et al, 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    HSP90 is involved in the maturation of several oncogenic client proteins, the degradation of which could abrogate cell growth and induce apoptosis.

    “HSP90 is involved in the maturation of several oncogenic client proteins, the degradation of which could abrogate cell growth and induce apoptosis (Maloney and Workman, 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Maloney and Workman, 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    5-fluorouracil has led to a small benefit in survival.

    “Traditionally used for nearly 50 years, 5-fluorouracil (5-FU) has led to a small benefit in survival (Buyse et al, 1988).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Buyse et al, 1988 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    C1A is mechanistically novel, with a mechanism of action more in keeping with the HDAC6 selective inhibitor tool-compound tubastatin A.

    “we show that C1A is mechanistically novel with a mechanism of action more in keeping with the HDAC6 selective inhibitor tool-compound tubastatin A.”
    Quote in the paperSubstantial claim
34 of 34

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Gene-expression percentage is stated as both less than and equal to 0.065%

    Minor

    The abstract says fewer than 0.065% of genes were modulated, but the results report 13 of 20,000 genes, which is exactly 0.065%.

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Authors
Kaliszczak, M., Trousil, S., Åberg, O., Perumal, M., Nguyen, Q.-D., & Aboagye, E. O.
Affiliations
Hammersmith Hospital (GB)
Corresponding author
Aboagye, E O
ORCID
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2013-01-15
Volume
108
Issue
2
Pages
342-350
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/bjc.2012.576
PMC
PMC3566806
OpenAlex
W2016460059
Semantic Scholar
95835246adf26652c8103cf941319dc0460a370a
Cited by
66
References
52
Citations by year
2025: 1 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 4 · 2014: 6 · 2013: 2
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Cancer (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Cancer Research UK (10337)
  • National Institute for Health and Care Research (C2536/A10337)
  • Imperial College London
  • Medical Research Council (C2536/A10337)
  • Engineering and Physical Sciences Research Council (C2536/A10337)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
HDAC6 inhibitors, hydroxamate, histone deacetylase, solid tumors, apoptosis, cell proliferation, alpha-tubulin acetylation, HSP90, vorinostat, 18F-fluorothymidine PET, gene expression modulation
MeSH terms
Histone Deacetylase 6, Acetylation, Animals, Cell Cycle, Female, Histone Deacetylases, Humans, Hydroxamic Acids, Mice, Inbred BALB C, Mice, Nude, Neoplasms, Tubulin, Gene Expression, Apoptosis, HSP90 Heat-Shock Proteins, Ki-67 Antigen, Xenograft Model Antitumor Assays, HCT116 Cells, Cell Proliferation, Mice, Caspase 3, Histone Deacetylase Inhibitors

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