Apoptosis In Human Osteosarcoma Cells Research Articles

Reversine inhibits proliferation and induces apoptosis of human osteosarcoma cells through targeting MEK1

Reversine, or 2-(4-morpholinoanilino)-6-cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule shows anti-tumor potential by playing a central role in the inhibition of several kinases related to cell cycle regulation and cytokinesis. In this study, systematic review demonstrated the feasibility and pharmacological mechanism of anti-tumor effect of reversine. Firstly, we grafted MNNG/HOS, U-2 OS, MG-63 osteosarcoma cell aggregates onto chicken embryonic chorioallantoic membrane (CAM) to examine the tumor volume of these grafts after reversine treatment. Following culture, reversine inhibited the growth of osteosarcoma cell aggregates on CAM significantly. In vitro experiment, reversine suppressed osteosarcoma cell viability, colony formation, proliferation, and induced apoptosis and cell cycle arrest at G0-G1 phase. Scratch wound assay demonstrated that reversine restrained cell migration. Reversine increased the protein expression of E-cadherin. The mRNA expression of Rac1, RhoA, CDC42, PTK2, PXN, N-cadherin, Vimentin in MNNG/HOS, U-2 OS and MG-63 cells were suppressed and PTEN increased after reversine treatment. Network pharmacology prediction, molecular docking and systematic review revealed MEK1 can be used as an effective target for reversine to inhibit osteosarcoma. Western blot results show the regulation of MEK1 and ERK1/2 by reversine was not consistent in different osteosarcoma cell lines, but we found that reversine significantly inhibited the protein expression of MEK1 in MNNG/HOS, U-2 OS and MG-63. All these suggested that reversine can exert its anti-tumor effect by targeting the expression of MEK1.

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.

Targeting PERK-ATF4-P21 axis enhances the sensitivity of osteosarcoma HOS cells to Mppα-PDT.

Osteosarcoma (OS) is the most prevalent type of malignant bone tumor in adolescents. The overall survival of OS patients has reached a plateau recently. Thus, there is an urgent need to develop approaches to improve the sensitivity of OS to therapies. Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPα-PDT) is a new type of tumor therapy, and elucidating its mechanism is helpful to improve its anti-tumor efficacy. Here, we investigated how PERK signaling promotes the human OS (HOS) cell survival induced by MPPα-PDT, as overcoming this may enhance sensitivity to MPPα-PDT. We found that MPPα-PDT combined with PERK inhibitor GSK2656157 enhanced HOS cell apoptosis by suppressing autophagy and p21. Autophagy inhibition and p21 depletion enhanced cell death, indicating pro-survival effects in MPPα-PDT. Notably, p21 was found to be an effector of the PERK-Atf4 pathway, which could positively regulate autophagy mediated by MPPα-PDT. In conclusion, we found that the combination of MPPα-PDT and GSK2656157 enhanced apoptosis in HOS cells by inhibiting autophagy. Mechanistically, this autophagy is p21-dependent and can be suppressed by GSK2656157, thereby enhancing sensitivity to MPPα-PDT.

Gambogenic acid induces cell death in human osteosarcoma through altering iron metabolism, disturbing the redox balance, and activating the P53 signaling pathway

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents with extremely poor prognosis. Gambogenic acid (GNA), one of the major bioactive ingredients isolated from Gamboge, has been shown to possess a multipotent antitumor effect, its activity on OS remains unclear yet. In this study, we found that GNA could trigger multiple cell death modalities, including ferroptosis and apoptosis in human OS cells, reduce the cell viability, inhibit the proliferation and invasiveness. Furthermore, GNA provoked oxidative stress leading to GSH depletion-inducing ROS generation and lipid peroxidation, altered iron metabolism represented by the induction of labile iron, mitochondrial membrane potential decreased, mitochondrial morphological changed, decreased the cell viability. In addition, ferroptosis inhibitors (Fer-1) and apoptosis inhibitors (NAC) can partially reversed GNA’ s effects on OS cells. Further investigation showed that GNA augmented the expression of P53, bax, caspase 3 and caspase 9 and decreased the expression of Bcl-2, SLC7A11 and glutathione peroxidase-4 (GPX4). In vivo, GNA was showed to delay tumor growth significantly in axenograft osteosarcoma mouse model. In conclusion, this study reveals that GNA simultaneously triggers ferroptosis and apoptosis in human OS cells by inducing oxidative stress via the P53/SLC7A11/GPX4 axis.

Echinatin inhibits the growth and metastasis of human osteosarcoma cells through Wnt/β-catenin and p38 signaling pathways

Osteosarcoma (OS) is a highly aggressive malignant bone tumor that mainly occurs in adolescents. At present, chemotherapy is the most commonly used method in clinical practice to treat OS. However, due to drug resistance, toxicity and long-term side effects, chemotherapy can’t always provide sufficient benefits for OS patients, especially those with metastasis and recurrence. Natural products have long been an excellent source of anti-tumor drug development. In the current study, we evaluated the anti-OS activity of Echinatin (Ecn), a natural active component from the roots and rhizomes of licorice, and explored the possible mechanism. We found that Ecn inhibited the proliferation of human OS cells and blocked cell cycle at S phase. In addition, Ecn suppressed the migration and invasion, while induced the apoptosis of human OS cells. However, Ecn had less cytotoxicity against normal cells. Moreover, Ecn inhibited the xenograft tumor growth of OS cells in vivo. Mechanistically, Ecn inactivated Wnt/β-catenin signaling pathway while activated p38 signaling pathway. β-catenin over-expression and the p38 inhibitor SB203580 both attenuated the inhibitory effect of Ecn on OS cells. Notably, we demonstrated that Ecn exhibited synergistic inhibitory effect with cisplatin (DDP) on OS cells in vitro and in vivo. Therefore, our results suggest that Ecn may exert anti-OS effects at least partly through regulating Wnt/β-catenin and p38 signaling pathways. Most meaningfully, the results obtained suggest a potential strategy to improve the DDP-induced tumor-killing effect on OS cells by combining with Ecn.

Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway.

Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway.

Isoquercitrin restrains the proliferation and promotes apoptosis of human osteosarcoma cells by inhibiting the Wnt/β-catenin pathway

Currently, chemotherapeutic drugs are widely used for the treatment of osteosarcoma. However, many of these drugs exhibit shortcomings such as poor efficacy, high toxicity, and tolerance. Isoquercitrin (ISO) is a traditional Chinese medicine that has been proved to exert good therapeutic effects on various tumors; however, its role in osteosarcoma has not been reported. Here, we observed that ISO exerted a marked inhibitory effect on the occurrence and development of osteosarcoma in a time- and dose-dependent manner. First, we determined that ISO significantly inhibited proliferation, induced EMT-related migration and invasion and induced apoptosis of osteosarcoma cells in vitro. Concurrently, we also observed that both β-catenin and its downstream genes (c-Myc, CyclinD1, and Survivin) were significantly down-regulated. To verify if the anti-tumor effect of ISO was related to the Wnt/β-catenin signaling pathway, we altered the protein expression level of β-catenin using recombinant lentivirus, then we observed that the effects of ISO on the proliferation, metastasis, and apoptosis of osteosarcoma cells were significantly reversed. Additionally, we used a nude mouse xenograft model and observed that ISO significantly inhibited the growth of osteosarcoma and improved the survival rate of the animal models. In conclusion, this study demonstrates that ISO can exert anti-tumor effects in part by inhibiting the Wnt/β-catenin signaling pathway, thus providing a new potential therapeutic strategy for the treatment of osteosarcoma.

Retraction: MicroRNA-182 downregulates Wnt/β-catenin signaling, inhibits proliferation, and promotes apoptosis in human osteosarcoma cells by targeting HOXA9.

[This retracts the article DOI: 10.18632/oncotarget.21167.].

Andrographolide inhibits the growth of human osteosarcoma cells by suppressing Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathways

Osteosarcoma (OS) is an aggressive malignant skeletal tumor characterized by an extremely poor prognosis and a high tendency to recur. The frequently used anti-OS chemotherapy regents are often limited by drug resistance and severe adverse events. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. Andrographolide (AG), a diterpenoid lactone isolated from Andrographis paniculata, has been proved to possess anti-tumor activity against several human cancer types. In this current study, we evaluated the inhibitory effect of AG on human OS cells and probed the possible mechanism. We found that AG inhibited the proliferation of human OS cells and blocked cell cycle at G2/M phase. Furthermore, AG impeded the migration and invasion, while promoted the apoptosis of human OS cells. Moreover, we found that AG inhibited OS growth and lung metastasis in orthotopic transplantation model. Mechanistically, we demonstrated that AG suppressed the activity of Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathways. Notably, we validated that AG synergized with the inhibitors of Wnt/β-catenin, PI3K/AKT and NF-κB to suppress the proliferation, migration and invasion of human OS cells. Collectively, our study conclusively demonstrates that AG inhibits the growth of human OS cells, thus, may be a promising candidate for the treatment of OS.

Lentivirus-induced knockdown of IARS2 expression inhibits the proliferation and promotes the apoptosis of human osteosarcoma cells.

Isoleucyl-tRNA synthetase 2 (IARS2), distributed in mitochondria, is an IARS involved in protein synthesis. Notably, IARS2 has been reported to be associated with tumor progression; however, the relationship between osteosarcoma (OS) and IARS2 remains unclear. To investigate the role of IARS2 in human OS, the expression and relationship of IARS2 with survival were firstly analyzed using the Gene Expression Profiling Interactive Analysis 2 database. Subsequently, an IARS2-short hairpin RNA lentiviral vector was established and used to infect the MNNG/HOS and U2OS cell lines. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were applied to determine the efficiency of IARS2 knockdown. The effects of IARS2 knockdown on cell proliferation, colony formation and apoptosis were evaluated by Celigo, MTT assays, colony formation assays and flow cytomeric analysis. In the present study, IARS2 tends to be high expressed in OS tissue and was associated with survival but this was not significant. The results of RT-qPCR and western blotting showed that the expression of IARS2 was effectively knocked down in the MNNG/HOS and U2OS cell lines. Celigo, MTT and colony formation assays showed that IARS2 knockdown in MNNG/HOS and U2OS cell lines inhibited cell proliferation and colony formation compared with in the control group. Flow cytometric analysis revealed that IARS2 knockdown increased apoptosis. These results suggested that IARS2 may be critical for the proliferation and apoptosis of OS cells.

Application of Novel Nano-Hydroxyapatite in Proliferation and Apoptosis of Human Osteosarcoma Cells

In this study, the purpose is to examine the impact of nano-hydroxyapatite (Nano-HAP) on human osteosarcoma cell (U2OS) growth and apoptosis (cell death). For reaching this goal an apoptosis kit was employed to determine the influence of Nano-HAP on apoptosis in human osteosarcoma cells U2OS, which were treated with different doses of Nano-HAP; FDA staining was used to elucidate the effect of Nano-HAP on cell adhesion. U2OS adhesion was not affected by Nano-HAP at different concentrations, however the production of U2OS was dramatically reduced. U2OS osteosarcoma cell growth was considerably inhibited at the doses of 50 g/ml and 800 g/ml, respectively. In conclusion, osteosarcoma cell growth and apoptosis are greatly inhibited by nano-HAP, although there is no clear linear link between nanoparticle concentration and the impact.

Protocatechuic Acid Induces Apoptosis in Human Osteosarcoma Cells by Regulating P13K/AKT/ROS Pathway

Previous investigations have demonstrated that protocatechuic acid (PCA) provides anti-tumour properties in different tumour cell types. It does, however, have an unknown cause on osteosarcoma cells. In this investigation, the underlying mechanism of the effect of PCA on osteosarcoma cells (MNNG or HOS) was investigated and established. The viability of the cell was assessed with the MTT test. Acridine orange/ethidium bromide staining and Western blot analysis were conducted for assessment of cell apoptosis. Western blot analysis was identified for cell cycle progression. In addition to establishing the above findings, the Western blot analysis demonstrated that PCA mediated osteosarcoma cellular apoptosis by triggering the apoptotic pathway of Caspase-9. Additionally, we found that PCA considerably stimulated osteosarcoma cell apoptosis and arrest of cell cycle proliferation by controlling a pathway involving P13K/Akt/ROS signalling. In short, we observed that PCA prevented the advancement of osteosarcoma through the stimulation of apoptosis in osteosarcoma cells. The mechanism underlying this study also showed that PCA generated effective anti-tumour activity on osteosarcoma cells by controlling the signalling pathways of P13K/Akt/ROS.

Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

BackgroundDiosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown.MethodsColony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells.ResultsDiosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules.ConclusionsThese results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

Sestrin2-Mediated Autophagy Contributes to Drug Resistance via Endoplasmic Reticulum Stress in Human Osteosarcoma.

One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.

Expression of Concern.

Expression of Concern.

Analysis and Construction of a Competitive Endogenous RNA Regulatory Network of Baicalin-Induced Apoptosis in Human Osteosarcoma Cells.

Background Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. Methods In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. Results Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). Conclusions By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.

Geranylgeranylacetone promotes human osteosarcoma cell apoptosis by inducing the degradation of PRMT1 through the E3 ubiquitin ligase CHIP.

Geranylgeranylacetone (GGA), an inducer of heat shock proteins, exerts anticancer activity in some tumours. However, the effect of GGA on human osteosarcoma (OS) has not been reported. This work is designed to evaluate the effect of GGA on the proliferation and apoptosis of human OS cells and to explore the underlying mechanisms. It was found that GGA markedly inhibited the proliferation and induced apoptosis of U‐2 OS cells in a dose‐dependent manner and also up‐regulated the expression of heat shock protein 70 (Hsp70). The degradation and ubiquitination of protein arginine N‐methyltransferase 1 (PRMT1) were obviously enhanced in U‐2 OS cells with CHIP overexpression and GGA treatment. The expression of PRMT1 was reversed in GGA‐treated cell after CHIP knockdown. The turnover of PRMT1 was obviously faster in cells overexpressing CHIP than that in control cells. The methylation and activity of STAT3 were induced by PRMT1, resulting in the inhibition of FAS transcription. Overexpression of PRMT1 reversed the effect of GGA on activation of apoptosis‐related proteins and U‐2 OS cell apoptosis. The expressions of PRMT1 were significantly up‐regulated in OS tissues compared with the adjacent normal tissues and benign bone tumours. In conclusion, GGA promotes the degradation of PRMT1 through the Hsp70‐CHIP‐mediated proteasome pathway, thereby inducing the FAS‐triggered cell apoptosis. Inhibition of PRMT1 may be a potential therapeutic strategy for OS patients.

Retraction.

Retraction: "Nimotuzuma restrains proliferation and induces apoptosis in human osteosarcoma cells by regulation of EGFR/PI3K/AKT signal pathway," by Meihan Liu, Jingzhe Zhang, Hang Dong, Wenjun Wang, J Cell Physiol. 2019; 20879-20887: The above article, published online on 18 April 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28693), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

7,8-Dihydroxyflavone suppresses proliferation and induces apoptosis of human osteosarcoma cells.

Recent studies suggest that 7,8-dihydroxyflavone (7,8-DHF) inhibits the development of several tumors. However, its role in osteosarcoma (OS) remains unknown. This study was designed to investigate the effects and underlying mechanisms of 7,8-DHF that may influence OS development. Human OS cell lines (U2OS and 143B) were treated with 7,8-DHF; cell viability and cell migration were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and wound-healing assay, respectively; and cell death and apoptosis were evaluated by LIVE/DEAD staining and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. Reactive oxygen species production was measured using 2,7-dichlorodihydrofluorescein diacetate probe. Akt, Bcl-xL/Bcl-2 asociated death promoter (Bad), p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) expression and their respective phosphorylation levels were detected by western blot analysis. We found that 7,8-DHF reduced cell viability in a dose-dependent manner and also promoted apoptosis, inhibited migration, and induced oxidative stress in OS cells. Moreover, 7,8-DHF inhibited Akt, Bad, and p38MAPK, but activated ERK and JNK signals. In summary, our results suggest that 7,8-DHF inhibits OS progression, possibly by regulating Akt/Bad and MAPK signaling. These findings provide new evidence for the pharmacological effects of 7,8-DHF that may improve drug therapy for OS patients.