RESUMO
Although cancer belongs to one of the leading causes of death around the world, fortunately studies have shown that tumor cells have various targets that are susceptible to attack. Interestingly, tumor cells are comprised of cellular membranes, which are altered in chemical composition relative to non-neoplastic cells, giving them an increased net negative charge. These altered membranes are ideal targets for antimicrobial peptides (AMPs) shown to have additional tumoricidal properties and, hence, named anticancer peptides (ACPs). Several hundred ACPs have been explored in vitro and in vivo on various types of cancer. Novel anticancer agents are supposed not to cause serious side effects and the formation of multidrug-resistant tumor cells. During the quest for potent ACPs, promising candidates were isolated from skin secretions of amphibians, such as the granular glands of the Chinese brown frog, Rana chensinensis. ACPs have to be selective to cancer cells and should not induce strong immune responses or be cleared from the body rapidly. Several modifications can improve ACPs either by optimizing the primary structure rationally or randomly or even by introducing other chemical modifications.
Assuntos
Anfíbios , Antineoplásicos/farmacologia , Peptídeos/farmacologia , Animais , Antineoplásicos/química , Peptídeos/química , Relação Estrutura-AtividadeRESUMO
Diurnal patterns of gene transcription are often conferred by complex interactions between circadian clock control and acute responses to environmental cues. Arabidopsis thaliana GIGANTEA (GI) contributes to photoperiodic flowering, circadian clock control, and photoreceptor signaling, and its transcription is regulated by the circadian clock and light. We used phylogenetic shadowing to identify three evolutionarily constrained regions (conserved regulatory modules [CRMs]) within the GI promoter and show that CRM2 is sufficient to confer a similar transcriptional pattern as the full-length promoter. Dissection of CRM2 showed that one subfragment (CRM2-A) contributes light inducibility, while another (CRM2-B) exhibits a diurnal response. Mutational analysis showed that three ABA RESPONSE ELEMENT LIKE (ABREL) motifs in CRM2-A and three EVENING ELEMENTs (EEs) in CRM2-B are essential in combination to confer a high amplitude diurnal pattern of expression. Genome-wide analysis identified characteristic spacing patterns of EEs and 71 A. thaliana promoters containing three EEs. Among these promoters, that of FLAVIN BINDING KELCH REPEAT F-BOX1 was analyzed in detail and shown to harbor a CRM functionally related to GI CRM2. Thus, combinatorial interactions among EEs and ABRELs confer diurnal patterns of transcription via an evolutionarily conserved module present in GI and other evening-expressed genes.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Regiões Promotoras Genéticas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Proteínas de Arabidopsis/metabolismo , Sequência de Bases , Sítios de Ligação/genética , Relógios Circadianos , Ritmo Circadiano , Sequência Conservada , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Evolução Molecular , Genoma de Planta/genética , Luz , Dados de Sequência Molecular , Mutação , Motivos de Nucleotídeos/genética , Plantas Geneticamente Modificadas , Ligação Proteica , Elementos de Resposta/genética , Homologia de Sequência do Ácido Nucleico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos da radiaçãoRESUMO
Curcumin, the extract of the rhizome of Curcuma longa, is known for its health-promoting properties in traditional medicine. It has anti-inflammatory, antitumor and antioxidant properties and stimulates appetite. In the present study, we investigated the stability of curcumin and its effect on cytotoxicity, apoptosis and melanin content in melanoma cells and the effect on atrophic C2C12 muscle cells. Cytotoxicity of curcumin was dose-dependent and the EC50 for 24-h incubation was 69 µM. Saturation was reached at 30 µM for a 48-h incubation. The EC50 for 24-h incubation with degraded curcumin solution was 116 µM and that for 48-h was 94 µM. Curcumin induced a strong increase in caspase-3/7 activity at 30-40 µM. Electrical impedance measurements showed that sub-toxic doses of curcumin counteracted atrophy in an in vitro model system. These findings indicate not only the positive effects of curcumin on melanoma cells in vitro, but also that curcumin was able to considerably trigger anti-cachectic effects in vitro. However, the importance of the stability of curcumin and its tumoricidal and anti-cachectic potential might play a pivotal role in its use in the nutrition and health industrie since it degrades rapidly in aqueous solutions.
