Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy

Pellerito, Claudia; Morana, Ornella; Ferrante, Francesco; Calvaruso, Giuseppe; Notaro, Antonietta; Sabella, Selenia; Fiore, Tiziana

doi:10.1016/j.jinorgbio.2015.06.001

Cited by 14 publications

(11 citation statements)

References 39 publications

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“…Another in vitro study on breast cancer reported the accumulation of acetylated histone proteins after incubation with CAPE, suggesting its HDAC inhibitory properties [333]. More recent evidence demonstrated a time-dependent reduction of global DNA methylated status induced by caffeic acid accompanied by a concomitant reduction of DNMT1 expression level [334].…”

Section: Polyphenolsmentioning

confidence: 99%

In Search of Panacea—Review of Recent Studies Concerning Nature-Derived Anticancer Agents

et al. 2019

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Cancers are one of the leading causes of deaths affecting millions of people around the world, therefore they are currently a major public health problem. The treatment of cancer is based on surgical resection, radiotherapy, chemotherapy or immunotherapy, much of which is often insufficient and cause serious, burdensome and undesirable side effects. For many years, assorted secondary metabolites derived from plants have been used as antitumor agents. Recently, researchers have discovered a large number of new natural substances which can effectively interfere with cancer cells’ metabolism. The most famous groups of these compounds are topoisomerase and mitotic inhibitors. The aim of the latest research is to characterize natural compounds found in many common foods, especially by means of their abilities to regulate cell cycle, growth and differentiation, as well as epigenetic modulation. In this paper, we focus on a review of recent discoveries regarding nature-derived anticancer agents.

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Section: Polyphenolsmentioning

confidence: 99%

In Search of Panacea—Review of Recent Studies Concerning Nature-Derived Anticancer Agents

et al. 2019

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“…For a long time, we have been involved in organotin(IV) complex synthesis, characterization, and biological studies to test their potential anti-tumor efficacy [ 11 , 12 , 13 , 14 , 15 , 16 ]. The leitmotiv has been the modulation of the intrinsic organometallic moiety cytotoxicity by means of biologically related molecules (synthetic or natural).…”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies have clearly shown that organotin complexes with valproic acid, another HDAC inhibitor, exert a remarkable antitumor action in hepatocarcinoma cells, as well as the dibutyltin(IV) complex of caffeic acid [ 13 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Tributyltin(IV) Butyrate: A Novel Epigenetic Modifier with ER Stress- and Apoptosis-Inducing Properties in Colon Cancer Cells

et al. 2021

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Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (1H, 13C and 119Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric environment similar to ester. FTIR and NMR findings confirm this structure both in solid state and solution. The antitumor efficacy of the triorganotin(IV) butyrates was tested in colon cancer cells and, among them, tributyltin(IV) butyrate (BT2) was selected as the most efficacious. BT2 induced G2/M cell cycle arrest, ER stress, and apoptotic cell death. These effects were obtained using low concentrations of BT2 up to 1 μM, whereas butyric acid alone was completely inefficacious, and the parent compound TBT was poorly effective at the same treatment conditions. To assess whether butyrate in the coordinated form maintains its epigenetic effects, histone acetylation was evaluated and a dramatic decrease in acetyl-H3 and -H4 histones was found. In contrast, butyrate alone stimulated histone acetylation at a higher concentration (5 mM). BT2 was also capable of preventing histone acetylation induced by SAHA, another potent HDAC inhibitor, thus suggesting that it may activate HDACs. These results support a potential use of BT2, a novel epigenetic modulator, in colon cancer treatment.

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“…Indeed, tin-based compounds can bind some membrane and cytoplasmic proteins such as receptors and glycoproteins, can cross lipid bilayer membranes and reach the nucleus, where they can directly interact with the DNA bases through intercalation, can also interact with the functional groups of the DNA grooves and with the phosphate of the DNA phosphodiester backbones as anchoring sites for the tin [11][12][13]. The consequences of these interactions are both the structural and functional alterations of the membranes and the induction of DNA damage that leads to the blockage of cell division and cell growth of organotin(IV)-treated cancer cells [6,[8][9][10][14][15][16]. Moreover, the ligand molecules of the organotin(IV) complexes, modifying the reactivity, the lipophilicity, the configuration and the molecular structure of the complexes and therefore their binding activity and functions, play a significant role in modulating the anti-tumour activity of the organotin(IV) moieties [12,17].…”

Section: Introductionmentioning

confidence: 99%

Dibutyltin(IV) and Tributyltin(IV) Derivatives of meso-Tetra(4-sulfonatophenyl)porphine Inhibit the Growth and the Migration of Human Melanoma Cells

Costantini

Leo

Sano

et al. 2019

Cells

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Melanoma is the most aggressive and deadly form of skin cancer, which is largely due to its propensity to metastasize. Therefore, with the aim to inhibit the growth and the metastatic dissemination of melanoma cells and to provide a novel treatment option, we studied the effects of the melanoma treatment with two organotin(IV) complexes of the meso-tetra(4-sulfonato-phenyl)porphine, namely (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS. In particular, we showed that nanomolar concentrations of (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS are sufficient to inhibit melanoma cell growth, to increase the expression of the full-length poly (ADP-ribose) polymerase (PARP-1), to induce the cell cycle arrest respectively at G2/M and G0/G1 through the inhibition of the Cyclin D1 expression and to inhibit cell colony formation. Nanomolar concentrations of (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS are also sufficient to inhibit the melanoma cell migration and the expression of some adhesion receptors. Moreover, we report that (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS act downstream of BRAF, mainly bypassing its functions, but targeting the STAT3 signalling protein. Finally, these results suggest that (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS may be effective therapeutic strategies for their role in the inhibition of melanoma growth and migration.

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Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy

Cited by 14 publications

References 39 publications

In Search of Panacea—Review of Recent Studies Concerning Nature-Derived Anticancer Agents

In Search of Panacea—Review of Recent Studies Concerning Nature-Derived Anticancer Agents

Tributyltin(IV) Butyrate: A Novel Epigenetic Modifier with ER Stress- and Apoptosis-Inducing Properties in Colon Cancer Cells

Dibutyltin(IV) and Tributyltin(IV) Derivatives of meso-Tetra(4-sulfonatophenyl)porphine Inhibit the Growth and the Migration of Human Melanoma Cells

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