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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.

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PURPOSE: Long-term human immunodeficiency virus (HIV)-infected patients are considered at higher risk for osteoporosis. Among the various causes that lead these patients to lower bone health, there is the use of antiretroviral drugs (ARVs), especially protease inhibitors (PI), such as ritonavir (RTV). In this context, emerge the potential benefits of LED therapy, whose effects on bone cells are currently being extensively studied, showing a modulation in cell differentiation. However, it remains unclear if photobiostimulation might interfere with RTV effects on osteoblast differentiation. METHODS: In the present study, we investigated the effects of red LED (625 nm) irradiation (15 mW/cm2, 0.2 J/cm2, and 8 mW/cm2, 0.12 J/cm2) on osteoblast cell line MC3T3-E1 treated with RTV (2.5, 5, and 10 µg/mL). RESULTS: Our results indicated that red LED irradiation was able to reverse, or at least minimize, the deleterious effects of RTV on the osteoblasts. Neither the ARV treatments 5 and 10 µg/mL (104.4% and 95.01%) nor the LED protocols (100.3% and 105.7%) statistically altered cell viability, assessed by the MTT assay. Also, the alkaline phosphatase activity and mineralization showed a decrease in osteoblast activity followed by ARV exposure (39.3-73%), which was attenuated by LED in more than 70% with statistical significance (p < 0.05). CONCLUSION: In conclusion, photobiostimulation with red LED at 625 nm was associated with improved beneficial biological effects as a potential inducer of osteogenic activity on RTV-affected cells. This is the first study that investigated the benefits of red LED irradiation over ARV-treated in vitro osteoblasts.

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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.

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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.

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The cellular response to surfaces is mediated, among other factors, by the extracellular matrix (ECM). However, little is known about the ECM proteome during mineralization. Our objective was to compare the ECM composition formed by osteoblast on different materials surfaces with proteomic analysis. Three types of biomaterial surfaces (pure titanium, anodized titanium, and zirconia) were used. Osteoblasts (MC3T3 linage) cells were cultivated on the biomaterials for 7, 14, and 21 days with the osteogenic medium. For the proteomic analysis, the specimens were washed, decellularized, and the ECM was collected. The majority of the typical ECM proteins, out of a total of 24 proteins identified, was expressed and regulated equally on the three biomaterials tested. Alpha-1,4 glucan phosphorylase was found to be down-regulated on zirconia on the seventh day, while at the same time, glycogen phosphorylase brain form was up-regulated on anodized titanium, both when compared with pure titanium (ratio: 1.06 and 0.97, respectively). And after 14 days of culture, glycogen phosphorylase brain form was downregulated on zirconia when compared with pure titanium (ratio: 0.90), suggesting the influence of material surface roughness and chemical composition on energy metabolism. Proteins related to bone development like Transforming growth factor beta-3 and Fibroblast growth factor 8 were found exclusively on pure titanium on the 21st day. Altogether, our results show a possible influence of material surfaces on the composition of ECM.

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Osteosarcoma is the most common type of bone cancer, and metastasis is widespread decreasing the survival rate. The search for new therapeutic strategies has increased for phytochemicals due to their potential as antioxidants and anticancer properties. Thus, we evaluated the caffeic acid phenethyl ester (CAPE) and caffeic acid's (CA) anticancer properties on UMR-106 murine osteosarcoma cells. The IC25 and IC50 were 1.3 and 2.7 µM for CAPE and 91.0 and 120.0 µM for CA, respectively. This study shows the potential anticancer properties of CAPE and highlights how a phenethyl ester component addition can improve the pharmacological potency in relation to its precursor CA. Our results showed that CAPE was more efficient and selective in reducing the viability of tumor cells compared to the control osteoblasts (MC3T3-E1) (p < 0.05). In addition, CAPE was 44-fold (IC25) and 70-fold (IC50) more cytotoxic than CA. CAPE also decreased ROS generation and cell migration. In summary, CAPE was more selective for tumor cells, preserving normal ones, suggesting its potential role as an anticancer drug.

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