Human Osteosarcoma Research Articles

Tumor treating fields suppress tumor cell growth and neurologic decline in models of spinal metastases.

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts and exposed to TTFields. Following TTFields exposure, the bioluminescence imaging (BLI) signal decreased to 10%-80% of baseline, while control cultures displayed a 4.48- to 9.36-fold increase in signal. Lastly, TTFields were applied in an orthotopic murine model of spinal metastasis. After 21 days of treatment, control mice demonstrated a 5-fold increase in BLI signal compared with TTFields-treated mice. TTFields similarly prevented tumor invasion into the spinal canal and development of neurologic symptoms. Our data suggest that TTFields can be leveraged as a local therapy within minimally conductive bone of spinal metastases. This provides the groundwork for future studies investigating TTFields for patients with treatment-refractory spinal metastases.

Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR-II Fluorescence Imaging.

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

Inhibition of proliferation of human osteosarcoma cell line (MG63) by ajwain (Trachyspermum ammi L.) plant extract

Trachyspermum ammi L. (TA), popularly called ajwain, is a well-known spice plant, with fruit pods that are used in Indian traditional medicine. Fruits of this plant were scientifically investigated for medicinal properties, but no studies are reported on the vegetative parts of the plant. Hence, the present investigation is aimed to evaluate the aerial parts of the plant for anti-proliferative and antioxidant effects. Methanolic extract (Me) of TA was subjected to sequential fractionation using the solvents in the increasing order of polarity viz. hexane (He), dichloromethane (Dcm), ethyl acetate (Ea), n-butanol (n-Bu), and water (Aq). Phytochemical analyses, DPPH radical scavenging assay, and in vitro antiproliferative activity on the MG63 osteosarcoma cell line (MTT assay) were performed. Preliminary phytochemical analyses revealed the presence of reducing and non-reducing sugars, amino acids, tannins, phenols, terpenoids, and saponins. Ethyl acetate fraction showed the highest amount of total phenolics (367.90±0.02), followed by n-Bu (287.50±0.04), Dcm (193.56±0.07), Me extract (190.14±0.07), Aq (142.20±0.02) and He (80.74±0.01) fractions. Ethyl acetate fraction exhibited higher DPPH radical scavenging activity (IC50 =116.74 μg/mL) followed by n-Bu (IC50=133.81 μg/mL) fraction with a correlation to the higher amount of phenolics and flavonoids. However, maximum antiproliferative activity was exhibited by hexane fraction on MG 63 human osteosarcoma cell line which can be attributed to the presence of thymol, a monoterpenoid phenol present in ajwain. The current study indicates that the aerial parts of T. ammi Linn. can be considered as potential antioxidants and therapeutic against osteosarcoma.

Retracted] miR‑34a is downregulated in human osteosarcoma stem‑like cells and promotes invasion, tumorigenic ability and self‑renewal capacity.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion assay data shown in Fig.4B on p.1635 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had either already been published or were submitted at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 15: 1631‑1637, 2017; DOI: 10.3892/mmr.2017.6187].

Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening

Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction ≤ 5%) among the 579 cell features measured at concentrations ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure–activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.

Low-energy shock waves promote the cisplatin chemosensitivity of human osteosarcoma MNNG/HOS cells via the P2X7/Akt/mTOR pathway.

The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors' results showed that 400 SW pulses at 0.21mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

Promising Dual Anticancer and Antimetastatic Action by a Cu(II) Complex Derived from Acylhydrazone on Human Osteosarcoma Models.

Osteosarcoma cancers are becoming more common in children and young adults, and existing treatments have low efficacy and a very high mortality rate, making it pressing to search for new chemotherapies with high efficacy and high selectivity index. Copper complexes have shown promise in the treatment of osteosarcoma. Here, we report the synthesis, characterization, and anticancer activity of [Cu(N-N-Fur)(NO3)(H2O)] complex where N-N-Fur is (E)-N'-(2-hydroxy-3-methoxybenzylidene)furan-2-carbohydrazide. The [Cu(N-N-Fur)(NO3)(H2O)] complex was characterized via X-ray diffraction and electron spin resonance (ESR), displaying a copper center in a nearly squared pyramid environment with the nitrate ligand acting as a fifth ligand in the coordination sphere. We observed that [Cu(N-N-Fur)(NO3)(H2O)] binds to DNA in an intercalative manner. Anticancer activity on the MG-63 cell line was evaluated in osteosarcoma monolayer (IC50 2D: 1.1 ± 0.1 μM) and spheroids (IC50 3D: 16.3 ± 3.1 μM). Selectivity assays using nontumoral fibroblast (L929 cell line) showed that [Cu(N-N-Fur)(NO3)(H2O)] has selectivity index value of 2.3 compared to cis-diamminedichloroplatinum(II) (CDDP) (SI = 0.3). Additionally, flow cytometry studies demonstrated that [Cu(N-N-Fur)(NO3)(H2O)] inhibits cell proliferation and conveys cells to apoptosis. Cell viability studies of MG-63 spheroids (IC50 = 16.3 ± 3.1 μM) showed that its IC50 value is 4 times lower than for CDDP (IC50 = 65 ± 6 μM). Besides, we found that cell death events mainly occurred in the center region of the spheroids, indicating efficient transport to the microtumor. Lastly, the complex showed dose-dependent reductions in spheroid cell migration from 7.5 to 20 μM, indicating both anticancer and antimetastatic effects.

Cytotoxicity assessment and LC-MS profiling of Adansonia digitata on human gastric and osteosarcoma cancer cell lines

Adansonia digitata (Baobab) is a large, iconic tree with rich medicinal and nutritional values and its parts are used to treat various ailments. The leaves, which are edible, serve as food. In addition to its dietary use, studies on its anti-cancer properties and the specialised metabolites responsible for those properties are limited. Therefore, this study aims to characterise the anticancer properties and chemical constituents of A. digitata L. leaves. The activity of the aqueous extract was evaluated against mouse fibroblast (L929), human gastric (AGS) and osteosarcoma (MG-63) cancer cell lines using an in-vitro MTT assay. A Brine Shrimp Lethality Assay (BSLA) was performed to determine the cytotoxicity of A. digitata extract. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was employed to identify the major chemical constituents. The in-vitro MTT assay showed that the extract has anticancer potential by sensitising cell proliferation, as the IC50 values for mouse L929, AGS and MG-63 were obtained as 2923 ± 4.504, 190.9 ± 10.81 and 1834 ± 6.194 µg/mL, respectively. BSLA elicited that there was no lethality found up to 100 µg/mL. The LC-MS analysis showed the presence of catechin, vitexin, kaempherol glycoside, rutin, and other phytocompounds. Overall, this study indicated that the potential anticancer activity of the plant extract of A. digitata against AGS cell lines, in addition to its dietary use, may be significantly influenced by its specialised metabolites.

Analysis of Osteosarcoma Cell Lines and Patient Tissue Using a 3D In Vivo Tumor Model—Possible Effects of Punicalagin

Osteosarcomas are the most common primary malignant bone tumors and mostly affect children, adolescents, and young adults. Despite current treatment options such as surgery and polychemotherapy, the survival of patients with metastatic disease remains poor. In recent studies, punicalagin has reduced the cell viability, angiogenesis, and invasion in cell culture trials. The aim of this study was to examine the effects of punicalagin on osteosarcomas in a 3D in vivo tumor model. Human osteosarcoma biopsies and SaOs-2 and MG-63 cells, were grown in a 3D in vivo chorioallantoic membrane (CAM) model. After a cultivation period of up to 72 h, the tumors received daily treatment with punicalagin for 4 days. Weight measurements of the CAM tumors were performed, and laser speckle contrast imaging (LSCI) and a deep learning-based image analysis software (CAM Assay Application v.3.1.0) were used to measure angiogenesis. HE, Ki-67, and Caspase-3 staining was performed after explantation. The osteosarcoma cell lines SaOs-2 and MG-63 and osteosarcoma patient tissue displayed satisfactory growth patterns on the CAM. Treatment with punicalagin decreased tumor weight, proliferation, and tumor-induced angiogenesis, and the tumor tissue showed pro-apoptotic characteristics. These results provide a robust foundation for the implementation of further studies and show that punicalagin offers a promising supplementary treatment option for osteosarcoma patients. The 3D in vivo tumor model represents a beneficial model for the testing of anti-cancer therapies.

Potential Cytoprotective and Anti-Apoptotic Effect of Metamizole Alone and in Combination with Cytostatic Drugs Observed In Vitro in Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines.

Metamizole (dipyrone) is still a frequently used drug in human and veterinary medicine, especially for pain relief, sometimes also in osteosarcoma treatment. It has a very strong analgesic and antipyretic effect and weaker anti-inflammatory activity. Additionally, it has spasmolytic properties. It is used in many species, including dogs, cats, pigs, cattle, horses, and humans, in Europe, Canada, and South America. The aim of this study was to assess a potential synergism of metamizole as a non-steroidal anti-inflammatory drug with routinely used cytostatics (cisplatin, carboplatin, doxorubicin, and etoposide). In vitro studies were performed on a canine osteosarcoma D-17 cell line and a human U-2 OS cell line. We used the MTT method to assess cell viability, TUNEL staining to assess proapoptotic effects, and propidium iodide to analyse the cell cycle (potential arrest). The obtained results showed that metamizole at 50 μg/mL has potential cytoprotective and anti-apoptotic effects. Metamizole administered simultaneously with cytostatic drugs reduced their cytotoxic effect, which may suggest that such a combination of drugs used in the treatment of osteosarcoma may significantly reduce therapy effectiveness.

Comprehensive in vitro and in ovo assessment of cytotoxicity: Unraveling the impact of sodium fluoride, xylitol, and their synergistic associations in dental products.

Over the past several decades, dental health products containing fluoride have been widely employed to mitigate tooth decay and promote oral hygiene. However, concerns regarding the potential toxicological repercussions of fluoride exposure have incited continuous scientific inquiry. The current study investigated the cytotoxicity of sodium fluoride (NaF) and xylitol (Xyl), both individually and in combination, utilizing human keratinocyte (HaCaT) and osteosarcoma (SAOS-2) cell lines. In HaCaT cells, NaF decreased proliferation in a concentration-dependent manner and induced apoptosis-related morphological changes at low concentrations, whereas Xyl exhibited dose-dependent cytotoxic effects. The combination of NaF and Xyl reduced cell viability, particularly at higher concentrations, accompanied by apoptosis-like morphological alterations. Sub-cytotoxic NaF concentrations (0.2%) significantly affected caspase activity and the expression of pro-apoptotic genes. Conversely, Xyl demonstrated no discernible effect on these biological parameters. In SAOS-2 cells, NaF increased proliferation at high concentrations, contrasting with Xyl's concentration-dependent cytotoxic effects. The combination of NaF and Xyl had a minimal impact on cell viability. Sub-cytotoxic NaF concentrations did not influence caspase activity or gene expression, while Xyl induced dose-dependent morphological alterations, increased caspase activity, and upregulated pro-apoptotic gene expression. In ovo experiments on the chorioallantoic membrane (CAM) revealed that only NaF induced irritant effects, suggesting potential vascular adverse outcomes. This study advocates for the combined use of NaF and Xyl, highlighting their cytotoxicity benefits in healthy cells while maintaining safety considerations for tumor cells.

Osteogenic assessment of leukocyte platelet-rich fibrin and injectable platelet-rich fibrin in the human osteosarcoma MG - 63 cell line in chronic periodontitis patients: An in vitro study.

The burgeoning interest in implant and regenerative dental care has led to a notable upsurge in the utilization of regenerative modalities. The intent of the present investigation was to evaluate the osteogenic ability of two different concentrated platelet groups at various concentrations in the human osteosarcoma MG-63 cell line. Blood samples from 21 volunteers with chronic periodontitis were collected which were then centrifuged in accordance with the protocols of Choukroun et al. and Miron et al. to produce leukocyte- and platelet-rich fibrin (L-PRF) and injectable platelet-rich fibrin (I-PRF), respectively. Following MG-63 cell culture, the osteogenic ability of 0, 4%, and 20% concentrations of both L-PRF and I-PRF were determined using the real-time polymerase chain reaction assay. The results showed that 20% I-PRF (1.52 ± 0.24) and 4% L-PRF (1.42 ± 0.37) had the highest amount of bone morphogenetic protein 2 and osteocalcin, respectively. I-PRF appears to promote the initial differentiation of cells.

Retraction Note to: A New Co-Based Coordination Polymer with an N-Tripodal Ligand: Synthesis, Crystal Structure, and Inhibition of Human Osteosarcoma Cells

Retraction Note to: A New Co-Based Coordination Polymer with an N-Tripodal Ligand: Synthesis, Crystal Structure, and Inhibition of Human Osteosarcoma Cells

Vat photopolymerization 3D printing of yttria-stabilized ZrO2 ceramics: effects of a sintering additive (Na2O – 2SiO2), biocompatibility, and osteointegration

Effects of a liquid-phase sodium disilicate additive on the properties of ZrO2 ceramics containing 3 mol.% of Y2O3 and 2 wt% of Al2O3 are presented, including phase composition, microstructure, shrinkage, porosity, and bending strength. The distribution of elements along grain boundaries and the composition in a selected area of a lamella were investigated by transmission electron microscopy in pure and additive-containing samples. As a result of the introduction of the additive, sintering activity of the material increased, and the sintering temperature diminished down to 1150 °C. Thus, dense nanocrystalline materials with a crystallite size of 50–70 nm and a bending strength of up to 450 MPa were obtained. Optimized polymer-ceramic suspensions were used to produce objects with complex geometric shapes by 3D molding technology through layer-by-layer vat polymerization. According to in vitro assays, the obtained samples are nontoxic and cytocompatible with human osteosarcoma MG-63 cells, and according to in vivo experiments, are biocompatible and showing osseointegrative properties when implanted into the rat tibia.

Repurposing of Loperamide as a New Drug With Anticancer Activity for Human Osteosarcoma.

Osteosarcoma is an aggressive malignant bone tumor, with unfavorable outcomes in patients with metastatic and recurrent disease. To improve patient survival new treatment options are needed. By using the drug repurposing approach, which takes advantage of already approved drugs with non-oncology primary use, we investigated the activity of loperamide, a peripheral opiate receptor agonist, a drug widely used in clinical practice to treat acute non-specific and chronic diarrhea, on human osteosarcoma. Human osteosarcoma cell lines (143B, Saos-2, HOS and MG-63) and multidrug-resistant MG-63DXR30 cells were treated with loperamide. Proliferation and cell viability were determined by viable cell count and acid phosphatase assay. Loperamide activity on cell cycle and apoptosis induction were evaluated by flow cytometry and a luminescence assay testing caspase 3/7 activity, respectively. Loperamide significantly inhibited cell proliferation, through alteration of cell cycle profile at G0/G1 phase and apoptotic death in human osteosarcoma cells. Furthermore, loperamide significantly inhibited the growth of multidrug-resistant osteosarcoma cells. Our findings provide new perspectives for loperamide and its therapeutic repositioning for the treatment of osteosarcoma.

The Effect of Photodynamic Therapy Using 5-Aminolevulinic Acid in Bone and Soft Tissue Sarcoma Cells.

5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of protoporphyrin IX (PpIX). Following light irradiation, the PpIX generates reactive oxygen species (ROS) in the presence of oxygen. Increased ROS levels can cause apoptotic cell death and necrosis of targeted cancer cells. This study examined whether photodynamic therapy using 5ALA (5-ALA PDT) could be used as a potential adjuvant therapy for bone and soft tissue sarcomas. The human osteosarcoma (143B), mouse osteosarcoma (LM8), human fibrosarcoma cell (HT1080) cell lines were used. In vitro, cultured cells were exposed to 5-ALA at various concentrations followed by strobe scope light irradiation for 10 min as 5-ALA PDT. Cell viability was then measured. In vivo, each tumor cell line was inoculated subcutaneously into the backs of mice. In the 5-ALA PDT group, 5-ALA (250 mg/kg) was administered intraperitoneally followed by light irradiation. Change in tumor volume by 5-ALA PDT were primarily evaluated. In vitro, treatment of sarcoma cells with 100 and 200 μg/ml 5-ALA PDT significantly inhibited cell proliferation at 24 and 48 h compared with the group treated with 0 and 10 μg/ml 5-ALA PDT. In vivo, in all cell lines, a significant inhibition of the tumor volume was observed in the 5-ALA-PDT group as compared to that in control, strobe scope light, and 5-ALA groups. 5-ALA PDT effectively inhibited proliferation of bone and soft tissue sarcoma cell lines. Further in vivo research using other subtypes of bone and soft tissue sarcoma is warranted to confirm the applicability in the clinical setting.

Bio-functionalized carbon dots for signaling immuno-reaction of carcinoembryonic antigen in an electrochemical biosensor for cancer biomarker detection

Early diagnosis of cancer demands sensitive and accurate detection of cancer biomarkers in blood. Carbon dots (CDs) bio-functionalization with antibodies, peptides or aptamers have played significant role in cancer diagnosis and targeted cancer therapy. Herein, a biosensor for detection of cancer biomarker carcinoembryonic antigen (CEA) in blood serum has been designed using CDs bio-functionalized with HRP-conjugated CEA antibody (CUCDs@CEAAb2) as detection probe. CDs were synthesized by upscaling of cow urine, a nitrogen rich biomass waste, by hydrothermal method. Detection probe based on CDs resulted in 3.5 times higher sensitivity as compared to conventional electrochemical sandwich immunoassay. To further improve the sensor performance, hyper-branched polyethylenimine grafted poly amino aniline (PEI-g-PAANI) was used as the sensing interface, which enabled immobilization of higher amount of capture antibody. Detection of CEA in human blood serum coupled with wide linear range (0.5–50 ng/ml), good specificity, stability, reproducibility and low detection limit (10 pg/ml) signified the excellence of CUCDs based CEA immunosensor. CUCDs exhibited excitation wavelength dependent fluorescence property and showed strong blue emission under UV irradiation. MTT assay indicated that the material is not toxic towards human dental pulp stem cells (hDPSCs) and MG63 osteosarcoma cells (cell viability > 90%). The present study demonstrates a methodology for valorization of animal waste to a cost-effective carbon based functional nanomaterial for clinical detection of cancer biomarkers.

Mefenamic acid exhibits antitumor activity against osteosarcoma by impeding cell growth and prompting apoptosis in human osteosarcoma cells and xenograft mice model

The study investigates the anticancer activity of mefenamic acid against osteosarcoma, shedding light on its underlying mechanisms and therapeutic potential. Mefenamic acid exhibited robust inhibitory effects on the proliferation of MG-63, HOS, and H2OS osteosarcoma cells in a dose-dependent manner. Moreover, mefenamic acid induced cellular toxicity in MG63 cells, as evidenced by LDH leakage, reflecting its cytotoxic impact. Furthermore, mefenamic acid effectively suppressed the migration and invasion of MG-63 cells. Mechanistically, mefenamic acid induced apoptosis in MG-63 cells through mitochondrial depolarization, activation of caspase-dependent pathways, and modulation of the Bcl-2/Bax axis. Additionally, mefenamic acid promoted autophagy and inhibited the PI3K/Akt/mTOR pathway, further contributing to its antitumor effects. The molecular docking studies provide compelling evidence that mefenamic acid interacts specifically and strongly with key proteins in the PI3K/AKT/mTOR pathway, suggesting a novel mechanism by which mefenamic acid could exert anti-osteosarcoma effects. In vivo studies using a xenograft mouse model demonstrated significant inhibition of MG-63 tumor growth without adverse effects, supporting the translational potential of mefenamic acid as a safe and effective therapeutic agent against osteosarcoma. Immunohistochemistry staining corroborated the in vivo findings, highlighting mefenamic acid's ability to suppress tumor proliferation and inhibit the PI3K/AKT/mTOR pathway within the tumor microenvironment. Collectively, these results underscore the promising therapeutic implications of mefenamic acid in combating osteosarcoma, warranting further investigation for clinical translation and development.

Synthesized tin oxide nanoparticles promote apoptosis in human osteosarcoma cells

Complicated protocols have been used to tune the size of tin oxide nanoparticles (SnO2 NPs) in conventional chemical synthesis approaches. In this study, we addressed this issue through the combination of polarity solvent reduction and sonication as a potential strategy for optimizing the size of SnO2 NPs for anticancer applications. Then the anticancer activity and safety of synthesized SnO2 NPs on U-2OS human osteosarcoma cells and normal human osteoblast, NHOst, respectively, were assessed by several assays. SEM and TEM analyses revealed that synthesized SnO2 NPs had a spherical-shaped morphology with an average particle size of about 10 nm. FTIR result showed a broad absorption peak at 649 cm– 1, corresponding to the stretching vibration of the O–Sn–O bond. XRD analysis exhibited eight main peaks, revealing a tetragonal system of rutile-like structure. DLS study showed that synthesized SnO2 NPs had an average hydrodynamic size of 43.93 nm with a zeta potential value of −31.00 mV. Cellular assays displayed that SnO2 NPs mitigate the growth of U-2OS human osteosarcoma cells (IC50: 15.50 µg/mL) with partial cytotoxicity on normal osteoblasts. It was then discovered that SnO2 NPs triggered stress effects by raising the levels of LDH release, ROS, and MDA and lowering those of SOD, CAT activity, and GSH content. Also, it was discovered that SnO2 NPs activated both intrinsic and extrinsic signaling pathways mediated by MMP collapse, elevation of caspase-3, −9, −8 activities and corresponding mRNA, and upregulation of Bax/Bcl-2 mRNA ratio. Overall, this study found that extrinsic and mitochondrial apoptotic pathways can both be activated by synthesized SnO2 NPs to induce apoptosis in human osteosarcoma cells. This finding calls for additional research in the future.

Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy

BackgroundDiallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway. MethodsIn this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 μM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers. ResultsDATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells. ConclusionsThis study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.