RESUMEN
Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.
RESUMEN
Although the pathogenesis of Parkinson's Disease (PD) is not completely understood, there is a consensus that it can be caused by multifactorial mechanisms involving genetic susceptibility, epigenetic modifications induced by toxins and mitochondrial dysfunction. In the past 20 years, great efforts have been made in order to clarify molecular mechanisms that are risk factors for this disease, as well as to identify bioactive agents for prevention and slowing down of its progression. Nutraceutical products have received substantial interest due to their nutritional, safe and therapeutic effects on several chronic diseases. The aim of this review was to gather the main evidence of the epigenetic mechanisms involved in the neuroprotective effects of phenolic compounds currently under investigation for the treatment of toxin-induced PD. These studies confirm that the neuroprotective actions of polyphenols involve complex epigenetic modulations, demonstrating that the intake of these natural compounds can be a promising, low-cost, pharmacogenomic strategy against the development of PD.
Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/prevención & control , Polifenoles/farmacología , Nutrigenómica , Epigénesis Genética , Predisposición Genética a la EnfermedadRESUMEN
Epigenetic mechanisms such as DNA methylation (DNAm) have been associated with stress responses and increased vulnerability to depression. Abnormal DNAm is observed in stressed animals and depressed individuals. Antidepressant treatment modulates DNAm levels and regulates gene expression in diverse tissues, including the brain and the blood. Therefore, DNAm could be a potential therapeutic target in depression. Here, we reviewed the current knowledge about the involvement of DNAm in the behavioural and molecular changes associated with stress exposure and depression. We also evaluated the possible use of DNAm changes as biomarkers of depression. Finally, we discussed current knowledge limitations and future perspectives.
Asunto(s)
Biomarcadores/sangre , Depresión/tratamiento farmacológico , Depresión/genética , Metiltransferasas/antagonistas & inhibidores , Animales , Antidepresivos/farmacología , Encéfalo/metabolismo , Islas de CpG , Metilación de ADN/efectos de los fármacos , Depresión/sangre , Epigenómica , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Modelos Animales , Ratas , Ratas Wistar , Estrés PsicológicoRESUMEN
Triple-negative breast cancer is an aggressive disease frequently associated with resistance to chemotherapy. Evidence supports that small molecules showing DNA methyltransferase inhibitory activity (DNMTi) are important to sensitize cancer cells to cytotoxic agents, in part, by reverting the acquired epigenetic changes associated with the resistance to therapy. The present study aimed to evaluate if chemical compounds derived from propolis could act as epigenetic drugs (epi-drugs). We selected three phenolic acids (caffeic, dihydrocinnamic, and p-coumaric) commonly detected in propolis and the (-)-epigallocatechin-3-gallate (EGCG) from green tea, which is a well-known DNA demethylating agent, for further analysis. The treatment with p-coumaric acid and EGCG significantly reduced the cell viability of four triple-negative breast cancer cell lines (BT-20, BT-549, MDA-MB-231, and MDA-MB-436). Computational predictions by molecular docking indicated that both chemicals could interact with the MTAse domain of the human DNMT1 and directly compete with its intrinsic inhibitor S-Adenosyl-l-homocysteine (SAH). Although the ethanolic extract of propolis (EEP) did not change the global DNA methylation content, by using MS-PCR (Methylation-Specific Polymerase Chain Reaction) we demonstrated that EEP and EGCG were able to partly demethylate the promoter region of RASSF1A in BT-549 cells. Also, in vitro treatment with EEP altered the RASSF1 protein expression levels. Our data indicated that some chemical compound present in the EEP has DNMTi activity and can revert the epigenetic silencing of the tumor suppressor RASSF1A. These findings suggest that propolis are a promising source for epi-drugs discovery.