Menadione and protocatechuic acid: A drug combination with antitumor effects in murine osteosarcoma cells.

Osteosarcoma (OS) is a primary malignant bone tumor that has an abnormal expression of oncogenesis and tumor suppressors and causes dysregulation of various signaling pathways. Thus, novel therapeutic strategies for OS are needed to overcome the resistance of traditional treatments. This study evaluated the cytotoxic and anticancer effects of the association between menadione (MEN) and protocatechuic acid (PCA) in murine OS cells (UMR-106). The concentrations were 3.12 µM of isolated MEN, 500 µM of isolated PCA, and their associations. We performed cell viability assays, morphology modification analysis, cell migration by the wound-healing method, apoptosis by flow cytometry, reactive oxygen species (ROS) production, gene expression of NOX by RT-qPCR, and degradation of MMP-2 and 9 by zymography. Our results showed that the association of MEN+PCA was more effective in OS cells than the compounds alone. The association decreased cell viability, delayed cell migration, and decreased the expression of NOX-2 and ROS. In addition, the MEN+PCA association induced a slight increase in the apoptotic process. In summary, the association can enhance the compound's antitumor effects and establish a higher selectivity for tumor cells, possibly caused by significant mitochondrial damage and antioxidant properties.

Neuron-specific enolase at admission as a predictor for stroke volume, severity and outcome in ischemic stroke patients: a prognostic biomarker review.

An ideal blood biomarker for stroke should provide reliable results, enable fast diagnosis, and be readily accessible for practical use. Neuron-specific enolase (NSE), an enzyme released after neuronal damage, has been studied as a marker for brain injury, including cerebral infarction. However, different methodologies and limited sample sizes have restricted the applicability of any potential findings. This work aims to determine whether NSE levels at Emergency Department (ED) admission correlate with stroke severity, infarcted brain volume, functional outcome, and/or death rates. A systematic literature review was performed using PubMed, Embase, and Scopus databases. Each reviewer independently assessed all published studies identified as potentially relevant. All relevant original observational studies (cohort, case-control, and cross-sectional studies) were included. Eleven studies (1398 patients) met the inclusion criteria. Among these, six studies reported a significant correlation between NSE levels and stroke severity, while only one found no association. Four studies indicated a positive relationship between infarcted brain volume assessed by imaging and NSE levels, in contrast to the findings of only one study. Four studies identified an association related to functional outcome and death rates, while three others did not reach statistical significance in their findings. These data highlight that NSE levels at ED admissions proved to be a promising tool for predicting the outcome of ischemic stroke patients in most studies. However, they presented high discrepancies and low robustness. Therefore, further research is necessary to establish and define the role of NSE in clinical practice.

Exploring the effects of vanillin and divanillin on murine osteosarcoma cells: evaluation of cellular response and proteomic analysis.

The objective of this study was to evaluate the antitumor properties of vanillin and divanillin in murine bone tumour cells. The action of the compounds on the cell viability of the normal (MC3T3-E1) and the tumour cell line (UMR-106) was evaluated. Action of the compounds in colony formation, migration, and production of reactive oxygen species (ROS) in tumour cells were evaluated along with proteomic analysis. Both compounds affected the cell viability of normal and tumour cell lines, being divanillin the more effective. For UMR-106, both compounds reduced the cell viability by less than 50%. Vanillin inhibited the migration process, and divanillin decreased ROS production (p < 0.05). The proteomic analysis showed that both compounds acted in the expression of proteins involved in tumour progression. Our results suggest that vanillin and divanillin are effective drugs against murine bone tumour cells. They can be a promising alternative for the adjuvant treatment of bone cancer.

The dimerization of methyl vanillate improves its effect against breast cancer cells via pro-oxidant effect.

Phenolic phytochemicals are a group of organic compounds with potent antioxidant features but can also act as powerful pro-oxidants. These characteristics are effective in reducing metastatic potential in cancer cells, and this effect has been associated with reactive oxygen species (ROS). Methyl vanillate (MV) and its dimer, methyl divanillate (DMV), are potent antioxidants. In the present study, we investigated the effects of MV and DMV on breast cancer cell lines MCF-7 and MDA-MB-231 and compared the results using the non-tumor cell line HB4a. Our results indicated that the compounds performed a pro-oxidant action, increasing the generation of ROS. DMV decreased the viability cell, showing a higher apoptotic effect and inhibition of proliferation than MV on both cell lines, with significant differences between groups (p < 0.05). Some modulation of NOX4, NOX5, and DUOX were observed, but the results did not correlate with the intracellular production of ROS. The dimer showed more effectivity and pro-oxidant effect than MV, impacting cell line MCF-7 in higher extension than MDA-MB-231. In conclusion, and corroborating with reported works, the dimerization of natural phenolic compounds was associated with improved beneficial biological effects as a potential cytotoxic agent to tumor cells.

Evaluation of Myrcia bella in murine osteosarcoma cells: Effect of the extract and enriched fractions of tannins and flavonoids.

Myrcia bella Cambess (Myrtaceae) is an important and common plant, native to the Brazilian Cerrado, with cytotoxicity, antimicrobial, and antidiabetic properties. Therefore, the effects of crude hydroalcoholic extract (CE) and fractions of ellagitannins (ELT) and flavonoids (FV) from Myrcia bella leaves were evaluated in a UMR-106 murine osteosarcoma cells and MC3T3 (normal cell). Cell viability and migration, production of reactive oxygen species (ROS) and matrix metalloproteinase (MMP) -2 and -9 activities were evaluated. In general, CE (80 µg/mL), ELT (160 µg/mL) and FV (64 µg/mL) reduced cell viability (p < 0.05). FV (64 µg/mL) was more effective in inhibition of cell migration, ROS production, and MMP-2 activity when compared to CE and ELT. Myrcia bella a rich source of phenolic compounds and its fraction of flavonoids have cytotoxic effects on osteosarcoma cells, preserving the viability of normal osteoblasts. Due to its antioxidant capacity, flavonoid may be a new therapeutic strategy for cancer.