RESUMO
Gentiopicroside (Gp) and swertiamarin (Sm), secoiridoid glycosides commonly found in plants of the Gentianaceae family, differ in one functional group. They exhibit promising cytotoxic effects in cancer cell lines and overall protective outcomes, marking them as promising molecules for developing novel pharmaceuticals. To investigate potential variations in cellular sensitivity to compounds of similar molecular structures, we analyzed the mode of Gp and Sm induced cell death in human peripheral blood mononuclear cells (PBMCs) after 48 h of treatment. The lowest tested concentration that significantly reduces cell viability, 50 µM, was applied. Oxidative stress parameters were estimated by measuring the levels of prooxidative/antioxidative balance, lipid peroxidation products, and 8-oxo-7,8-dihydro-2-deoxyguanosine, while gene expression of DNA repair enzymes was evaluated by employing quantitative real-time PCR. Cellular morphology was analyzed by fluorescent microscopy, and immunoblot analysis of apoptosis and necroptosis-related proteins was used to assess the type of cell death induced by the treatments. The discriminatory impact of Gp/Sm treatments on apoptosis and necroptosis-induced cell death was evaluated by monitoring the cell survival in co-treatment with specific cell death inhibitors. Obtained results show greater cytotoxicity of Gp than Sm suggesting that variations in the molecular structures of the tested compounds can substantially affect their biological effects. Gp/Sm co-treatment with apoptosis and necroptosis inhibitors revealed a distinct, albeit non-specific mechanism of PBMCs cell death. Although the therapeutic may not directly cause a specific type of cell death, its extent can be pivotal in assessing the safety of therapeutic application and developing phytopharmaceuticals with improved features. Since phytopharmaceuticals affect all exposed cells, identification of cytotoxic mechanisms on PBMCs after Gp and Sm treatment is important for addressing the formulation and dosage of potential phytopharmaceuticals.
Assuntos
Apoptose , Sobrevivência Celular , Glucosídeos Iridoides , Leucócitos Mononucleares , Estresse Oxidativo , Pironas , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Glucosídeos Iridoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pironas/farmacologia , Pironas/química , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Cinamatos/farmacologia , Cinamatos/química , Peroxidação de Lipídeos/efeitos dos fármacosRESUMO
Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.
Assuntos
Carcinoma Hepatocelular , Nanismo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Oncogenes , CarcinogêneseRESUMO
PLA (polylactic acid) is one of the three major biopolymers available on the market for food packaging, which is both bio-based and biodegradable. However, its performance as a barrier to gases remains too weak to be used for most types of food, particularly oxygen-sensitive foods. A surface treatment, such as coating, is a potential route for improving the barrier properties and/or providing bioactive properties such as antioxidants. Gelatin-based coating is a biodegradable and food-contact-friendly solution for improving PLA properties. The initial adhesion of gelatin to the film is successful, both over time and during production, however, the coating often delaminates. Corona processing (cold air plasma) is a new tool that requires low energy and no solvents or chemicals. It has been recently applied to the food industry to modify surface properties and has the potential to significantly improve gelatin crosslinking. The effect of this process on the functional properties of the coating, and the integrity of the incorporated active compounds were investigated. Two coatings have been studied, a control fish gelatin-glycerol, and an active one containing gallic acid (GA) as a natural antioxidant. Three powers of the corona process were applied on wet coatings. In the test conditions, there were no improvements in the gelatin crosslinking, but the corona did not cause any structural changes. However, when the corona and gallic acid were combined, the oxygen permeability was significantly reduced, while free radical scavenging, reduction, and chelating properties remained unaffected or slightly improved.
RESUMO
BACKGROUND: Precise molecular characterization of breast cancer, especially triple negative (TNBC) as the most lethal subtype, is needed to stratify patients for the individual treatment approach. MicroRNA-205 (miR-205) has tumor-suppressive and oncogenic functions across different cancers. Therefore, miR-205 might have a different role in TNBC and estrogen receptor (ER) positive BC. Our aim was to investigate how miR-205 expression is associated with ER/progesteron receptor status, clinical parameters, pathohistological characteristics of BC, and survival of patients METHODS: We determined miR-205 relative expressions in 73 primary breast tumors (50 TNBC and 23 ER+) by quantitative Real-time polymerase chain reaction (qPCR) and compared it to clinicopathological characteristics and outcome. RESULTS: The highest levels of miR-205 were in the ER+ /PR+ group, and the lowest in the TNBC group (p = 0.009). Significantly higher levels of miR-205 were also observed in the ER+ compared with the ER-negative group, regardless of the PR status (p = 0.002). Low miR-205 expression level was associated with prognostic stage III in TNBC samples (p = 0.049). Patients who received adjuvant chemotherapy had significantly lower levels of miR-205 (p = 0.016). Patients who received hormone therapy had significantly higher levels of miR-205 (p = 0.007). The low-miR-205 patients had significantly higher 5-year survival rates (p = 0.041). CONCLUSION: The expression of miR-205 in BC is subtype-specific and high expression is associated with the ER+ tumors. The miR-205 expression might be a useful marker of TNBC progression. High miR-205 expression had a detrimental effect on BC patient outcome. Our results indicate that miR-205 might be utilized in clinical practice as a biomarker and an adjunct parameter for the selection of the most effective therapeutic modality.
RESUMO
The discovery of the Estrogen Receptor Beta (ERß) in 1996 opened new perspectives in the diagnostics and therapy of different types of cancer. Here, we present a review of the present research knowledge about its role in endocrine-related cancers: breast, prostate, and thyroid, and colorectal cancers. We also discuss the reasons for the controversy of its role in carcinogenesis and why it is still not in use as a biomarker in clinical practice. Given that the diagnostics and therapy would benefit from the introduction of new biomarkers, we suggest ways to overcome the contradictions in elucidating the role of ERß.
Assuntos
Neoplasias da Mama/patologia , Neoplasias Colorretais/patologia , Receptor beta de Estrogênio/metabolismo , Metástase Neoplásica/patologia , Neoplasias da Próstata/patologia , Neoplasias da Glândula Tireoide/patologia , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/patologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MasculinoRESUMO
The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ERß) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ERß gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ERß1 isoform, while ERß1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ERß gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ERα) protein levels (ρ = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ERß1 protein levels were negatively correlated with ERα protein (ρ = -0.27, P < 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ERß1-mRNA and/or protein levels.