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1.
Pharmacol Res ; 141: 512-520, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30641278

RESUMO

Caloric restriction (CR) has been shown to promote longevity and ameliorate aging-associated diseases, including cancer. Extensive research over recent decades has revealed that CR reduces IGF-1/PI3K/AKT signaling and increases sirtuin signaling. We recently found that CR also enhances ALDOA/DNA-PK/p53 signaling. In the present review, we summarize the molecular mechanisms underlying the modulation of the IGF-1/PI3K/AKT pathway, sirtuin signaling, and the ALDOA/DNA-PK/p53 pathway by CR. We also summarize the evidence concerning the roles of these signaling pathways in carcinogenesis, and discuss how they are regulated by CR. Finally, we discuss the crosstalk between these signaling pathways.


Assuntos
Restrição Calórica , Carcinogênese/metabolismo , Neoplasias/dietoterapia , Neoplasias/metabolismo , Transdução de Sinais , Animais , Restrição Calórica/métodos , Proteína Quinase Ativada por DNA/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias/prevenção & controle , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirtuínas/metabolismo , Proteína Supressora de Tumor p53/metabolismo
2.
Adv Exp Med Biol ; 818: 181-96, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25001537

RESUMO

Many of the pathologies associated with the aging process also contribute to tumor initiation, growth or metastasis. Insights from biogerontology may be instrumental for developing new therapies for cancer. This chapter highlights the rationale for combining biogerontology and cancer research to generate new strategies for cancer treatment. In particular, this chapter focuses on one gene, SIRT6, which has emerged as an important regulator of longevity in mammals and appears to have multiple biochemical functions, which antagonize tumor development and may be useful in cancer prevention and treatment.


Assuntos
Proteínas de Neoplasias , Neoplasias , Sirtuínas/metabolismo , Animais , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias/enzimologia , Neoplasias/patologia , Neoplasias/prevenção & controle
3.
Phytomedicine ; 129: 155673, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677274

RESUMO

BACKGROUND: Doxorubicin (DOX) is a widely utilized anthracycline chemotherapy drug in cancer treatment, yet its efficacy is hindered by both short-term and long-term cardiotoxicity. Although oxidative stress, inflammation and mitochondrial dysfunction are established factors in DOX-induced cardiotoxicity, the precise molecular pathways remain elusive. Further exploration of the pathogenesis and identification of novel molecular targets are imperative. Recent studies have implicated the Sirtuins family in various physiological and pathological processes, suggesting their potential in ameliorating DOX-induced cardiotoxicity. Moreover, research on Sirtuins has discovered small-molecule compounds or medicinal plants with regulatory effects, representing a notable advancement in preventing and treating DOX-induced cardiac injury. PURPOSE: In this review, we delve into the pathogenesis of DOX-induced cardiotoxicity and explore the therapeutic effects of Sirtuins in mitigating this condition, along with the associated molecular mechanisms. Furthermore, we delineate the roles and mechanisms of small-molecule regulators of Sirtuins in the prevention and treatment of DOX-induced cardiotoxicity. STUDY-DESIGN/METHODS: Data for this review were sourced from various scientific databases (such as Web of Science, PubMed and Science Direct) up to March 2024. Search terms included "Sirtuins," "DOX-induced cardiotoxicity," "DOX," "Sirtuins regulators," "histone deacetylation," among others, as well as several combinations thereof. RESULTS: Members of the Sirtuins family regulate both the onset and progression of DOX-induced cardiotoxicity through anti-inflammatory, antioxidative stress and anti-apoptotic mechanisms, as well as by maintaining mitochondrial stability. Moreover, natural plant-derived active compounds such as Resveratrol (RES), curcumin, berberine, along with synthetic small-molecule compounds like EX527, modulate the expression and activity of Sirtuins. CONCLUSION: The therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity represents a potential molecular target. However, further research is urgently needed to elucidate the relevant molecular mechanisms and to assess the safety and biological activity of Sirtuins regulators. This review offers an in-depth understanding of the therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity, providing a preliminary basis for the clinical application of Sirtuins regulators in this condition.


Assuntos
Cardiotoxicidade , Doxorrubicina , Sirtuínas , Sirtuínas/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/toxicidade , Cardiotoxicidade/prevenção & controle , Humanos , Animais , Estresse Oxidativo/efeitos dos fármacos , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/toxicidade
4.
J Cardiometab Syndr ; 4(2): 102-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19614797

RESUMO

Resveratrol (3,4',5 trihydroxystilbene), a naturally-occurring molecule known as a phytoalexin, is synthesized by plants in response to attacks by fungi, bacteria, or other injurious substances; it is also known to possess an array of cardioprotective effects. Recently, studies have shown resveratrol to protect against the metabolic changes associated with hypercaloric diets in mice with induced insulin resistance, hyperglycemia, and dyslipidemia. Despite impressive gains in diagnosis and treatment, cardiovascular disease (CVD) remains a serious clinical problem and threat to public health. The metabolic syndrome, which identifies persons at higher risk for diabetes mellitus and CVD, is approaching a prevalence of nearly 25% of the western world. If the metabolic syndrome can be considered a polar opposite to caloric restriction, then agents that mimic caloric restriction may offer a new therapeutic approach to preventing CVD. The authors discuss the cardioprotective effects of resveratrol and highlight its role in glucose homeostasis and lipid metabolism in mice. Armed with the ability to prevent the deleterious effects of excess caloric intake and prevent detrimental cardiovascular events, resveratrol merits proper clinical investigations for its efficacy in treating metabolic diseases and CVD.


Assuntos
Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/prevenção & controle , Síndrome Metabólica/tratamento farmacológico , Estilbenos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Restrição Calórica , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Carboidratos da Dieta/metabolismo , Gorduras na Dieta/metabolismo , Ingestão de Energia , Homeostase , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Estrutura Molecular , Resveratrol , Sirtuína 1 , Sirtuínas/metabolismo , Estilbenos/química , Estilbenos/uso terapêutico
5.
J Cosmet Dermatol ; 7(1): 2-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18254804

RESUMO

Resveratrol, an antioxidant polyphenol from red wine, has been the subject of intense interest in recent years due to a range of unique anti-aging properties. These include cardiovascular benefits via increased nitric oxide production, down-regulation of vasoactive peptides, lowered levels of oxidized low-density lipoprotein, and cyclooxygenase inhibition; possible benefits on Alzheimer's disease by breakdown of beta-amyloid and direct effects on neural tissues; phytohormonal actions; anticancer properties via modulation of signal transduction, which translates into anti-initiation, antipromotion, and antiprogression effects; antimicrobial effects; and sirtuin activation, which is believed to be involved in the caloric restriction-longevity effect. Here we report a resveratrol-based skin care formulation, with 17 times greater antioxidant activity than idebenone. The role of resveratrol in prevention of photoaging is reviewed and compared with other antioxidants used in skin care products.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Estilbenos/farmacologia , Doença de Alzheimer/prevenção & controle , Animais , Antioxidantes/uso terapêutico , Cardiopatias/prevenção & controle , Humanos , Resveratrol , Sirtuínas/metabolismo , Estilbenos/uso terapêutico , Vinho
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