RESUMO
Peptide-based cancer therapy has been of great interest due to the unique advantages of peptides, such as their low MW, the ability to specifically target tumour cells, easily available and low toxicity in normal tissues. Therefore, identifying and synthesizing novel peptides could provide a promising option for cancer patients. The antitumour second generation peptide, CIGB-552 has been developed as a candidate for cancer therapy. Proteomic and genomic studies have identified the intracellular protein COMMD1 as the specific target of CIGB-552. This peptide penetrates to the inside tumour cells to induce the proteasomal degradation of RelA, causing the termination of NF-κB signalling. The antitumour activity of CIGB-552 has been validated in vitro in different human cancer cell lines, as well as in vivo in syngeneic and xenograft tumour mouse models and in dogs with different types of cancers. The aim of this review is to present and discuss the experimental data obtained on the action of CIGB-552, including its mechanism of action and its therapeutic potential in human chronic diseases. This peptide is already in phase I clinical trials as antineoplastic drug and has also possible application for other inflammatory and metabolic conditions.
Assuntos
Antineoplásicos , Peptídeos Penetradores de Células , Neoplasias , Proteínas Adaptadoras de Transdução de Sinal , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cães , Caranguejos Ferradura , Humanos , Camundongos , Neoplasias/tratamento farmacológico , ProteômicaRESUMO
The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates, and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF-κB-mediated transcription, hypoxia induced transcription, DNA damage response, and oncogenesis. The present work reviews the molecular mechanisms and biological processes regulated by COMMD1 that have been described so far, emphasizing in the regulatory role of the protein and its importance for cellular homeostasis. J. Cell. Biochem. 119: 34-51, 2018. © 2017 Wiley Periodicals, Inc.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinogênese , Hipóxia Celular , Cobre , Reparo do DNA , Regulação da Expressão Gênica , NF-kappa B/metabolismo , Estresse Oxidativo , Agregação Patológica de Proteínas , Transcrição GênicaRESUMO
Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation.