The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment

Stiborová, Marie; Eckschlager, Tomáš; Poljaková, Jitka; Hraběta, Jan; Adam, Vojtěch; Kizek, René; Frei, Eva

doi:10.2174/092986712802884286

Cited by 66 publications

(56 citation statements)

References 228 publications

(290 reference statements)

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“…doxorubicin, epirubicin, etoposid, cisplatin, 5-fluorouracil, melphalan, and temozolomide and ionizing radiation in many cancer cell lines) (ref. 78 ).…”

Section: ) Promising Results Have Been Reported For Combinations Of mentioning

confidence: 99%

Histone deacetylase inhibitors in cancer therapy. A review

Hraběta¹,

Stiborová²,

Adam³

et al. 2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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a Background. Despite recent success toward discovery of more effective anticancer drugs, chemoresistance remains a major cause of treatment failure. There is emerging evidence that epigenetics plays a key role in the development of the resistance. Epigenetic regulators such as histone acetyltransferases (HATs) and histone deacetylases (HDACs) play an important role in gene expression. The latter are found to be commonly linked with many types of cancers and influence cancer development. Overall, histone acetylation is being investigated as a therapeutic target because of its importance in regulating gene expression. This review summarizes mechanisms of the anticancer effects of histone deacetylase (HDAC) inhibitors and the results of clinical studies. Results. Different HDAC inhibitors induce cancer cell death by different mechanisms that include changes in gene expression and alteration of both histone and non-histone proteins. Enhanced histone acetylation in tumors results in modification of expression of genes involved in cell signaling. Inhibition of HDACs causes changed expression in 2-10 % of genes involved in important biological processes. The results of experiments and clinical studies demonstrate that combination of HDAC inhibitors with some anticancer drugs have synergistic or additive effects. Conclusions. Even though many biological effects of HDAC inhibitors have been found, most of the mechanisms of their action remain unclear. In addition, their use in combination with other drugs and the combination regime need to be investigated. The discovery of predictive factors is also necessary. Finally, a key question is whether the pan-HDAC inhibitors or the selective inhibitors will be more efficient for different types of cancers.

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“…doxorubicin, epirubicin, etoposid, cisplatin, 5-fluorouracil, melphalan, and temozolomide and ionizing radiation in many cancer cell lines) (ref. 78 ).…”

Section: ) Promising Results Have Been Reported For Combinations Of mentioning

confidence: 99%

Histone deacetylase inhibitors in cancer therapy. A review

Hraběta¹,

Stiborová²,

Adam³

et al. 2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…12,19,20 Furthermore, DNA targeted chemotherapeutic agents showed synergistic or at least additive effects when combined with HDACIs. 21 Although the antitumor effect of HDACIs was demonstrated in many studies, it is widely accepted that HDACIs in combination with other antitumor drugs may be more effective than HDACI alone. In particular because HDACIs facilitate histone acetylation, resulting in the relaxation of chromatin structure, DNA damaging agents are considered to be good candidates to combine with HDACIs.…”

Section: Discussionmentioning

confidence: 99%

Combination Treatment of Renal Cell Carcinoma with Belinostat and 5-Fluorouracil: A Role for Oxidative Stress Induced DNA Damage and HSP90 Regulated Thymidine Synthase

et al. 2015

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In combination with 5-fluorouracil the targeted inhibitor of histone deacetylase synergistically inhibited renal cancer cell growth by the blockade of thymidylate synthase induction and the induction of reactive oxygen species mediated DNA damage in vitro and in vivo. Our results suggest that combined treatment with belinostat and 5-fluorouracil may represent a promising new approach to renal cancer.

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“…The HDACs are important for gene expression, and the levels of these enzymes are increased in tumor cells and differ according to cancer type [51,52]. For example, HDAC1 is highly expressed in prostate, gastric, lung, esophagus, and breast cancers.…”

Section: Butyrate In Epigenetic and Gene Expressionmentioning

confidence: 99%

Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment

Encarnação

Abrantes

Pires

et al. 2015

Cancer Metastasis Rev

101

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Colorectal cancer is still a major health problem worldwide. Based on the most recent released data by the World Health Organization GLOBOCAN in 2012, colorectal cancer is the third most prevalent type of cancer in males and the second in females. In 1999, it was published the first report showing evidence of a strong correlation between diet and cancer incidence, being its positive or negative impact intimately linked to dietary patterns. A diet rich in fiber is associated with a low risk of developing colorectal cancer. The fermentation of the dietary fiber by intestinal microflora results in production of butyrate, which plays a plurifunctional role on the colonocytes, and it has also been reported as a chemopreventive agent. However, there are limited studies focusing its anti-cancer potential. Here, we review the recent new insights that focus butyrate and its role in colorectal cancer prevention and treatment, from its synthesis, metabolism, and transport, through its involvement on several cancer-related signaling pathways, to the novel existing approaches for its clinical use.

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The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment

Cited by 66 publications

References 228 publications

Histone deacetylase inhibitors in cancer therapy. A review

Histone deacetylase inhibitors in cancer therapy. A review

Combination Treatment of Renal Cell Carcinoma with Belinostat and 5-Fluorouracil: A Role for Oxidative Stress Induced DNA Damage and HSP90 Regulated Thymidine Synthase

Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment

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