The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

Heidor, Renato; Furtado, Kelly Silva; Ortega, Juliana Festa; Oliveira, Tiago Franco de; Tavares, Paulo; Vieira, Antônio Wilson; Miranda, Mayara Lilian Paulino; Purgatto, Eduardo; Moreno, Fernando Salvador

doi:10.1016/j.taap.2014.02.004

Cited by 24 publications

(15 citation statements)

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“…These results are surprising since butyrate is usually thought of as a class I HDAC inhibitor (if not a pan HDAC inhibitor) that has both histone and non-histone targets, for example HMG protein in colon cancer cells 36, 37, 38 . Tributyrin and valproic acid (IC 50 : 39μM~2mM) are other small molecule HDAC inhibitors in the same category 39, 40, 41 . Tributyrin shares p21WAF1 as a common gene target for de-repression in cancer cells 41 .…”

Section: 0 Protein Acetylation and Dietary Chemopreventive Agentsmentioning

confidence: 99%

Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors

Kim¹,

Bisson²,

Löhr³

et al. 2015

CTMC

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Acetylation is an important, reversible post-translational modification affecting histone and non-histone proteins with critical roles in gene transcription, DNA replication, DNA repair, and cell cycle progression. Key regulatory enzymes include histone deacetylase (HDACs) and histone acetyltransferases (HATs). Overexpressed HDACs have been identified in many human cancers, resulting in repressed chromatin states that interfere with vital tumor suppressor functions. Inhibition of HDAC activity has been pursued as a mechanism for re-activating repressed genes in cancers, with some HDAC inhibitors showing promise in the clinical setting. Dietary compounds and their metabolites also have been shown to modulate HDAC activity or expression. Out of this body of research, attention increasingly has shifted towards non-histone targets of HDACs and HATs, such as transcriptions factors, hormone receptors, DNA repair proteins, and cytoskeletal components. These aspects are covered in present review, along with the possible clinic significance. Where such data are available, examples are cited from the literature of studies with short chain fatty acids, polyphenols, isoflavones, indoles, organosulfur compounds, organoselenium compounds, sesquiterpene lactones, isoflavones, and various miscellaneous agents. By virtue of their effects on both histone and non-histone proteins, dietary chemopreventive agents modulate the cellular acetylome in ways that are only now becoming apparent. A better understanding of the molecular mechanisms will likely enhance the potential to more effectively combat diseases harboring altered epigenetic landscapes and dysregulated protein signaling. Dietary chemopreventive agents modulate the cellular acetylome by affecting both histone and non-histone proteins, which will likely enhance their potential to more effectively combat diseases harboring altered epigenetic landscapes.

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Section: 0 Protein Acetylation and Dietary Chemopreventive Agentsmentioning

confidence: 99%

Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors

Kim¹,

Bisson²,

Löhr³

et al. 2015

CTMC

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“…132 Recent studies show that tributyrin protects carcinogen-treated rats against the development of colon cancer. 133 In addition, a study with carcinogen-treated mice showed a lower tumor incidence of 43% in tributyrin-fed mice compared with 60% in control mice. 134 Clarke et al 135 showed that carcinogen-treated rats fed a butyrylated starch diet had more apoptosis in the distal colon when compared with rats fed a control diet.…”

Section: Carcinogenesismentioning

confidence: 99%

The gut in control of health and disease

Beek¹

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“…A TB também induziu apoptose em linhagem de células de câncer gástrico XU, 2003), câncer de mama (HEERDT et al, 1999), câncer de cólon (CLARKE; FEINMAN; HARRISON, 2001) e de HCC (WATKINS et al, 1999), sendo considerada um agente quimiopreventivo promissor (GASCHOTT et al, 2001). Além disso, a atividade quimiopreventiva da TB foi observada na carcinogênese de cólon e fases iniciais da hepatocarcinogênese em animais (HEIDOR et al 2014). Estudos prévios em nosso laboratório demonstraram in vivo, que a TB apresentou atividade quimiopreventiva quando administrada durante as fases de iniciação e promoção (KUROIWA-TRZMIELINA et al, 2009;GUARIENTO et al, 2014;HEIDOR et al, 2016), bem como somente durante a fase de promoção da hepatocarcinogênese (DE CONTI et al, 2011).…”

Section: Quimioterapia E Quimioprevençãounclassified

Atividade anticarcinogênica da tributirina associada ou não ao sorafenibe em ratos Fischer-344 implantados com células GP7TB

Tavares¹

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Primary liver cancer (PLC) presents poor prognosis, which makes its chemoprevention important. In this sense, tributyrin (TB), a prodrug of butyric acid (AB), present in dairy products and honey, has been shown to be a promising chemopreventive agent for experimental hepatocarcinogenesis. The inhibitory effects of TB have been related to inhibition of the development of pre-neoplastic lesions, as well as induction of apoptosis and hyperacetylation of histones. Chemotherapy is one of the most common approaches for treating various types of cancer, including PLC. In this case, treatment with sorafenib (SO) is able to prolong the average survival of patients with the disease in advanced stages in approximately three months. In view of this, studies of the association of sorafenib with other compounds that may increase the efficacy of chemotherapeutic treatment are necessary. Thus, the association of anti-neoplastic drugs with bioactive compounds in food may be a potential strategy to increase efficacy against cancer. In the present study, the anticarcinogenic activity of TB and SO was evaluated, alone or in combination, in the progression stage of hepatocarcinogenesis. For this purpose, syngenic implants were performed on the flank of Fischer-344 mice from GP7TB tumor cells. When the neoplasms reached 1 cm 3 , the animals were randomized into experimental groups: Control group (CO), consisting of 10 Fischer 344 rats receiving Maltodextrin (300mg / 100 g.p.c), isocaloric control and 12.5% ethanol solution, and Cremofor to 12.5% in sterile water; Tributyrin group (TB), consisting of 9 Fischer 344 rats that received TB (200mg / 100 g.p.c.) and 12.5% ethanol solution and Cremofor 12.5% in sterile water; Sorafenib group (SO) consisting of 9 Fischer 344 rats receiving maltodextrin (300 mg / 100 g, w / w), isocaloric control and sorafenib tosylate (3 mg / 100 g, w / w) in sterile water; The association group of tributyrin and sorafenib (AS) consisted of 9 Fischer 344 rats receiving TB (20 mg / 100 g p.o.) and sorafenib tosylate (3 mg / 100 g p.o.); treated intragastric (i.g) daily for 5 consecutive weeks. The concentrations of AB and SO were analyzed by gas chromatography associated with mass spectrometry and the neoplasms were characterized by immunohistochemistry. In relation to the evolution of the size of the neoplasias, the AS group presented smaller (p = 0.009) size of the same ones in relation to the CO group. However, these differences did not reach significant differences (p> 0.05) between the TB and CO groups, as well as between the SO and CO groups. However, when adjusted for size of the neoplasm by latency, significant changes (p <0.05) were observed in the different groups when compared to the CO group. The SO group increased the necrotic area of the neoplasias, although this difference did not reach a significant difference (p> 0.05), while the TB group reduced this necrotic area in relation to the CO group (p = 0.005). The TB and AS groups presented significantly higher (p <0.05) hepatic and neoplastic AB co...

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The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

Cited by 24 publications

References 48 publications

Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors

Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors

The gut in control of health and disease

Atividade anticarcinogênica da tributirina associada ou não ao sorafenibe em ratos Fischer-344 implantados com células GP7TB

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