RESUMO
Spermine, spermidine and putrescine polyamines are naturally occurring ubiquitous positively charged amines and are essential metabolites for biological functions in our life. These compounds play a crucial role in many cell processes, including cellular proliferation, growth, and differentiation. Intracellular levels of polyamines depend on their biosynthesis, transport and degradation. Polyamine levels are high in cancer cells, which leads to the promotion of tumor growth, invasion and metastasis. Targeting polyamine metabolism as an anticancer strategy is considerably rational. Due to compensatory mechanisms, a single strategy does not achieve satisfactory clinical effects when using a single agent. Combination regimens are more clinically promising for cancer chemoprevention because they work synergistically with causing little or no adverse effects due to each individual agent being used at lower doses. Moreover, bioactive substances have advantages over single chemical agents because they can affect multiple targets. In this review, we discuss anticancer strategies targeting polyamine metabolism and describe how combination treatments and effective natural active ingredients are promising therapies. The existing research suggests that polyamine metabolic enzymes are important therapeutic targets and that combination therapies can be more effective than monotherapies based on polyamine depletion.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Homeostase/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Poliaminas/antagonistas & inibidores , Poliaminas/metabolismo , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Humanos , Poliaminas/químicaRESUMO
MAIN CONCLUSION: Accumulation of specific metabolites, mainly γ-aminobutyric acid, polyamines, and proline, was essential to homeostasis regulation and differential salt tolerance in sorghum genotypes. Salinity is severe abiotic stress that limits plant growth and development in arid and semi-arid regions. Survival to abiotic stresses depends on metabolic and sometimes even morphological adjustments. We measured the growth parameters, water relations, the content of ions (Na+, K+, Cl-), compatible solutes [some free amino acids (FAAs) including γ-aminobutyric acid (GABA) and proline and soluble carbohydrates) and polyamines (PAs), the activity of PAs metabolism enzymes, and metabolomic profile in plants after 14 days of salt stress treatment. These analyses were to evaluate the influence of metabolomic responses of sorghum genotypes exhibiting sensitivity (CSF18) or tolerance (CSF20) to salinity on plant growth. The salinity promoted growth reductions and induced increases in Na+ and Cl- content and decreases in K+ content. The water status and osmotic potential (Ψo) were reduced by salt stress, but to minimize damage, especially in the CSF20, the osmolytes and PAs contributed to the osmotic adjustment. The results showed that salinity induced an increase in putrescine (Put) in the sensitive genotype. However, it raised spermidine (Spd), spermine (Spm), and cadaverine (Cad) in the tolerant genotype. In addition, the regulation of polyamine oxidase can be related to Spm and GABA biosynthesis. Differential metabolic changes to salt tolerance include metabolites associated with tricarboxylic acid (TCA) cycle intermediates and the metabolisms of sugars, FAAs, and PAs.
Assuntos
Desenvolvimento Vegetal/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Tolerância ao Sal/genética , Tolerância ao Sal/fisiologia , Sorghum/genética , Sorghum/metabolismo , Variação Genética , Genótipo , Desenvolvimento Vegetal/fisiologia , Estresse Salino/genética , Estresse Salino/fisiologiaRESUMO
Human and bovine trichomoniasis are sexually transmitted diseases (STD) caused by Trichomonas vaginalis and Tritrichomonas foetus, respectively. Human trichomoniasis is the most common non-viral STD in the world and bovine trichomoniasis causes significant economic losses to breeders. Considering the significant impact of the infections caused by these protozoa and the treatment failures, the search for new therapeutic alternatives becomes crucial. In this study the effect of diamines and amino alcohols in the in vitro viability of trichomonads was evaluated. Screening demonstrated the high activity of diamine 4 against these protozoa. Although cytotoxicity against HMVII cell line and slight hemolysis were observed in vitro, the compound showed no toxic effect on the Galleria mellonella in vivo model. Importantly, diamine 4 was active against both trichomonads species at 6h and 24h of incubation, and these effects was reverted by putrescine, a polyamine, suggesting competition for the same metabolic pathway. These findings indicate that the mechanism of action of diamine 4 is through the polyamine metabolism, a pathway distinct from that presented by metronidazole, the drug usually used to treat trichomoniasis and to which resistance is widely reported. These data demonstrate the importance of diamines as potential novel candidates as anti-T. vaginalis and anti-T. foetus agents.