Paeoniflorin induces G2/M cell cycle arrest and caspase-dependent apoptosis through the upregulation of Bcl-2 X-associated protein and downregulation of B-cell lymphoma 2 in human osteosarcoma cells.

Paeoniflorin (PF), extracted from the peony root, has been proved to possess antineoplastic activity in different cancer cell lines. However, it remains unclear whether PF has an antineoplastic effect against osteosarcoma cells. The present study investigated the effects and the specific mechanism of PF on various human osteosarcoma cell lines. Using the multiple methods to detect the activity of PF on HOS and Saos­2 human osteosarcoma cell lines, including an MTS assay, flow cytometry, transmission electron microscopy and western blotting, it was demonstrated that PF induces inhibition of proliferation, G2/M phase cell cycle arrest and apoptosis in the osteosarcoma cell lines in vitro, and activation of cleaved­caspase­3 and cleaved­poly (ADPribose) polymerase in a dose­dependent manner. Furthermore, the pro­apoptotic factors Bcl­2 X­associated protein and BH3 interacting domain death agonist were uregulated, while the anti­apoptotic factors B­cell lymphoma 2 (Bcl­2) and Bcl­2­extra large were downregulated. In conclusion, these results demonstrated that PF has a promising therapeutic potential in for osteosarcoma.

Tetrandrine induces apoptosis and triggers a caspase cascade in U2-OS and MG-63 cells through the intrinsic and extrinsic pathways.

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.

Do we really need tranexamic acid in total hip arthroplasty? A meta-analysis of nineteen randomized controlled trials.

BACKGROUND: Studies have shown that tranexamic acid reduces blood loss and transfusion need in patients undergoing total hip arthroplasty. However, no to date, no study has been large enough to determine definitively whether the drug is safe and effective. We examined whether intravenous tranexamic acid, when compared with placebo, was safe and effective in total hip arthroplasty. METHODS: The literature search was conducted using the PubMed, Cochrane Library, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. Data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. Ultimately, 19 randomized controlled trials involving 1,030 patients were included. RESULTS: The use of tranexamic acid significantly reduced total blood loss by a mean of 305.27 mL [95 % confidence interval (CI) -397.66 to -212.89, p < 0.001], intraoperative blood loss by a mean of 86.33 mL(95 % CI -152.29 to -20.37, p = 0.01), postoperative blood loss by a mean of 176.79 mL (95 % CI -236.78 to -116.39, p < 0.001), and "hidden" blood loss by a mean of 152.70 mL (95 % CI -187.98 to -117.42, p < 0.001), resulting in a meaningful reduction in the proportion of patients requiring blood transfusion (odds ratio 0.28, 95 % CI 0.19 to 0.42, p < 0.001). There was no significant difference in occurrence of deep vein thrombosis, pulmonary embolism, or other complications among the study groups, or cost or hospitalization duration. CONCLUSIONS: The data from this meta-analysis indicate that intravenous tranexamic acid may reduce blood loss and transfusion need in patients undergoing total hip arthroplasty without increasing the risk of complications. However, high-quality randomized controlled trials are required to validate the results.

Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.

Gambogic acid (GA), the natural product, has been demonstrated to be a promising chemotherapeutic drug for osteosarcoma (OS) due to its ability to induce apoptosis and cell cycle arrest. To date, no studies have examined the role of GA in metastatic bone disease. Matrix metalloproteinases (MMPs) play critical roles in invasion and metastasis, and the tissue inhibitors of metalloproteinase (TIMP) family regulates the activity of multifunctional metalloproteinases. In this study, we investigated the gene expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in OS cell lines treated by the GA. The expression of MMP-9 and TIMP-1 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. In vitro invasion of OS cell lines (Saos-2, MG-63) were investigated by the Matrigel invasion assay. Mean MMP-9 protein and mRNA expression was significantly suppressed; in addition, mean TIMP-1 protein mRNA expression were upregulated by increasing GA concentrations. GA reduced the invasiveness of OS cell lines dose-dependently. Furthermore, specific inhibition of TIMP-1 secretion with siRNA against TIMP-1 significantly reduced the effect of GA on OS cell lines. Overall, our findings suggest that GA reduces the invasive potential of OS cells via attenuation of MMP-9 and upregulation of TIMP-1. Moreover, TIMP-1 played an important role in the reduction of invasive potential of the OS cells which were treated by GA.

Gallic acid induces the apoptosis of human osteosarcoma cells in vitro and in vivo via the regulation of mitogen-activated protein kinase pathways.

To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.