Histone deacetylase inhibitors require caspase activity to induce apoptosis in lung and prostate carcinoma cells

Sonnemann, Jürgen; Hartwig, Maite; Plath, Andrea; Kumar, Kusum; Müller, Cornelia; Beck, James F.

doi:10.1016/j.canlet.2005.02.009

Cited by 40 publications

(29 citation statements)

References 29 publications

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“…In particular, the role of caspases in suberoylanilide hydroxamic acid-induced apoptosis is controversial. Suberoylanilide hydroxamic acid-induced apoptosis has been shown to be caspase-dependent in acute promyelocytic leukemia (13,15), head and neck squamous carcinoma (17), breast cancer (14), lung, and prostate carcinomas (16). In contrast, Ruefli et al (19) have shown that suberoylanilide hydroxamic acid induces caspase-independent apoptosis in acute T-cell leukemia cells.…”

Section: Discussionmentioning

confidence: 94%

“…We have recently found HDAC2 overexpression in 86% of oral squamous cell carcinoma cases (12), providing a good reason for treating oral squamous cell carcinoma with HDACis. One of the HDACis, suberonylanilide hydroxamic acid, is an orally administered HDACi that has been shown to induce apoptosis in a variety of tumor cells, but the signaling pathways involved seems to be dependent on cell type and context (13)(14)(15)(16)(17)(18)(19). It is now in phase I and II clinical trials for the treatment of various malignancies and has shown anticancer effects at doses that are tolerated by the patients (11).…”

Section: Introductionmentioning

confidence: 99%

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Suberoylanilide hydroxamic acid sensitizes human oral cancer cells to TRAIL-induced apoptosis through increase DR5 expression

Yeh

Deng

Sha

et al. 2009

Molecular Cancer Therapeutics

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Suberoylanilide hydroxamic acid has been shown to selectively induce tumor apoptosis in cell cultures and animal models in several types of cancers and is about as a promising new class of chemotherapeutic agents. In addition, suberoylanilide hydroxamic acid showed synergistic anticancer activity with radiation, cisplatin, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in some cancers. Here, we report suberoylanilide hydroxamic acid also induced apoptosis in human oral cancer cells. Western blotting showed suberoylanilide hydroxamic acid increased Fas, Fas ligand, DR4, and DR5 protein expression and activated caspase-8 and caspase-9. The apoptosis was almost completely inhibited by caspase-8 inhibitor Z-IETD-FMK and attenuated by caspase-9 inhibitor Z-LEHD-FMK. Human recombinant DR5/Fc chimera protein but not Fas/Fc or DR4/Fc significantly inhibited apoptosis induced by suberoylanilide hydroxamic acid. These results suggest that suberoylanilide hydroxamic acid induces apoptosis mainly through activation of DR5/ TRAIL death pathway. Furthermore, subtoxic concentrations of suberoylanilide hydroxamic acid sensitize two TRAIL resistant human oral cancer cells, SAS and Ca9-22, to exogenous recombinant TRAIL-induced apoptosis in a p53-independent manner. Combined treatment of suberoylanilide hydroxamic acid and TRAIL may be used as a new promising therapy for oral cancer. [Mol Cancer Ther 2009;8(9):2718-25]

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Suberoylanilide hydroxamic acid sensitizes human oral cancer cells to TRAIL-induced apoptosis through increase DR5 expression

Yeh

Deng

Sha

et al. 2009

Molecular Cancer Therapeutics

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“…For example, HDIs have been shown to cooperate with the proteasome inhibitor bortezomib (22), and aspirin has been reported to inhibit proteasome function (23). Likewise, HDI-induced cell death can be augmented by inhibiting the antiapoptotic transcription factor NF-κB (24,25), whose activation is blocked by aspirin and salicylic acid (26,27). It is currently under discussion that salicylates and other NSAIDs in general may have synergistic efficacy when combined with anticancer agents (28,29).…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells

Sonnemann

Hüls²,

Sigler³

et al. 2008

Oncol Rep

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Abstract. Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1-and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy.

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“…INK4b , p21 WAF1/CIP1 , caspase-3 and the inducible orphan nuclear receptor Nur-77, whose expression is important in the induction of apoptosis and has recently been demonstrated to be abrogated in acute myeloid leukemia, whilst also down regulating Bcl-XL and MMPs in cell lines (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…HDACi have recently been described to have significant therapeutic activity in the treatment of hematological malignancies including cutaneous T-cell lymphoma, Hodgkin's lymphoma, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) (5). In vitro HDACi have been shown to up-regulate the expression of p15INK4b , p21 WAF1/CIP1 , caspase-3 and the inducible orphan nuclear receptor Nur-77, whose expression is important in the induction of apoptosis and has recently been demonstrated to be abrogated in acute myeloid leukemia, whilst also down regulating Bcl-XL and MMPs in cell lines (6)(7)(8)(9)(10)(11)(12)(13)(14).Numerous in vitro studies together with recent pre-clinical and early phase clinical studies identify significant antileukemic activity of a combination of HDACi with demethylating agents with greater inhibition of growth and DNA synthesis, and a greater loss of clonogenicity than that observed by single agent treatment in in vitro studies (14)(15)(16)(17)(18)(19)(20). However, the mechanisms of HDACi-induced cell death and underlying the anti-cancer synergy between HDACi and other agents are not completely understood.…”

mentioning

confidence: 99%

The anti-leukemic effect and molecular mechanisms of novel hydroxamate and benzamide histone deacetylase inhibitors with 5-aza-cytidine

Liu

Mayes²,

Perlmutter³

et al. 2011

Int J Oncol

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Abstract. Histone deacetylase inhibitors (HDACi) demonstrate considerable in vitro and in vivo activity and clinical efficacy in the treatment of hematological malignancies. Pre-clinical and early phase clinical trials identify therapeutic activity using a combination of HDACi and demethylating agents which may be more efficacious than single agent treatment. Our studies aimed to determine the effects and molecular mechanisms of action of novel hydroxamate (MCT-3) and benzamide [MGCD0103 (MG)] HDACi's in the HL-60 cell line alone and in combination with the demethylating agent 5-aza-cytidine (AZA). MG, MCT-3 and AZA treatment significantly inhibited HL-60 cell growth in vitro with MG being the most potent agent. MG in combination with AZA demonstrated no significant increase in inhibition of cell growth over MG treatment alone whilst MCT-3 in combination with AZA demonstrated increased inhibition of cell growth over either agent alone although no more significant than MG alone. MG alone or MCT-3 in combination with AZA significantly increased p15 and caspase-3 expression. MG and MCT-3 significantly attenuated AZA-induced MMP-9 mRNA expression and proteolytic activity. Interestingly, MCT-3, MG and AZA alone and in combination increased expression of the novel tumour suppressor gene Nur77, important in leukemogenesis, with MG a more potent inducer as a single agent. These observations suggest the enhanced anti-leukemia activity of the combination of AZA and HDACi may only reside with certain HDACi classes and may be in-part explained by regulation of genes associated with cell cycle arrest, apoptosis and tumour suppression. IntroductionHistone deacetylase inhibitors (HDACi) represent a novel, structurally heterogeneous class of compounds. The four chemical classes of HDACi, include the benzamides (e.g., MGCD0103), the hydroxamates (e.g., MCT-3, SAHA), the short-chain fatty acids (e.g., valproic acid), and the cyclic tetrapeptides (e.g., Depsipeptide/FK228) (1-4). The hydroxamates are frequently referred to as 'broad-spectrum' or 'pan'-HDACi resulting from inhibition of several HDAC isoforms). The remaining chemical classes of HDACi selectively inhibit class I HDACs (3,4). HDACi have recently been described to have significant therapeutic activity in the treatment of hematological malignancies including cutaneous T-cell lymphoma, Hodgkin's lymphoma, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) (5). In vitro HDACi have been shown to up-regulate the expression of p15INK4b , p21 WAF1/CIP1 , caspase-3 and the inducible orphan nuclear receptor Nur-77, whose expression is important in the induction of apoptosis and has recently been demonstrated to be abrogated in acute myeloid leukemia, whilst also down regulating Bcl-XL and MMPs in cell lines (6)(7)(8)(9)(10)(11)(12)(13)(14).Numerous in vitro studies together with recent pre-clinical and early phase clinical studies identify significant antileukemic activity of a combination of HDACi with demethylating agents with greater inhibition of growth and DNA...

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Histone deacetylase inhibitors require caspase activity to induce apoptosis in lung and prostate carcinoma cells

Cited by 40 publications

References 29 publications

Suberoylanilide hydroxamic acid sensitizes human oral cancer cells to TRAIL-induced apoptosis through increase DR5 expression

Suberoylanilide hydroxamic acid sensitizes human oral cancer cells to TRAIL-induced apoptosis through increase DR5 expression

Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells

The anti-leukemic effect and molecular mechanisms of novel hydroxamate and benzamide histone deacetylase inhibitors with 5-aza-cytidine

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