Morin inhibits osteosarcoma migration and invasion by suppressing urokinase plasminogen activator through a signal transducer and an activator of transcription 3.

Osteosarcoma, the most common primary bone cancer that affects adolescents worldwide, has the early metastatic potential to be responsible for high mortality rates. Morin has a multipurpose role in numerous cancers, whereas little is known about its role in osteosarcoma migration and invasion. Therefore, we hypothesized that morin suppresses the invasive activities and the migratory potential of human osteosarcoma cells.

Apoptotic effect and cell arrest of deoxyshikonin in human osteosarcoma cells through the p38 pathway.

Osteosarcoma is the most common primary bone cancer that affects adolescents with early metastatic potential and drastically reduces their long-term survival rate if pulmonary metastases are detected at diagnosis. The natural naphthoquinol compound deoxyshikonin exhibits anticancer properties, so we hypothesized that it has an apoptotic effect on osteosarcoma U2OS and HOS cells and studied its mechanisms. After deoxyshikonin treatment, dose-dependent decreases in cell viability, induction of cell apoptosis and arrest in the sub-G1 phase of U2OS and HOS cells were observed.

Curcumin and its Analogs and Carriers: Potential Therapeutic Strategies for Human Osteosarcoma.

Curcumin is a natural polyphenol phytochemical derived from turmeric with antioxidant, anti-inflammatory, and anticancer properties but is concerned about poor solubility in water, absorption, and metabolic stability. Potent metastatic osteosarcoma is the most common primary bone cancer in children, adolescents, and young adults. It is responsible for low survival rates because of its high rate of metastasis to the lungs.

Different molecular weights of hyaluronan research in knee osteoarthritis: A state-of-the-art review.

Osteoarthritis (OA), the most common form of arthritis, is characterized by progressive cartilage destruction, concomitant adaptive osteogenesis, and loss of joint function. The progression of OA with aging is associated with a decrease in native hyaluronan (HA, hyaluronate or hyaluronic acid) with a high molecular weight (HMW) in synovial fluid and a subsequent increase in lower MW HA and fragments. As HMW HA possesses numerous biochemical and biological properties, we review new molecular insights into the potential of HA to modify OA processes.

HO-3867 Induces Apoptosis via the JNK Signaling Pathway in Human Osteosarcoma Cells.

Metastatic osteosarcoma often results in poor prognosis despite the application of surgical en bloc excision along with chemotherapy. HO-3867 is a curcumin analog that induces cell apoptosis in several cancers, but the apoptotic effect and its mechanisms on osteosarcoma cells are still unknown. After observing the decrease in cellular viability of three human osteosarcoma U2OS, HOS, and MG-63 cell lines, and the induction of cellular apoptosis and arrest in sub-G1 phase in U2OS and HOS cells by HO-3867, the human apoptosis array showed that heme oxygenase (HO)-1 and cleaved caspase-3 expressions had significant increases after HO-3867 treatment in U2OS cells and vice versa for cellular inhibitors of apoptosis (cIAP)1 and X-chromosome-linked IAP (XIAP).

Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway.

Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential.

The potential remedy of melatonin on osteoarthritis.

Osteoarthritis (OA), the most common arthritis worldwide, is a degenerative joint disease characterized by progressive cartilage breakdown, subchondral remodeling, and synovial inflammation. Although conventional pharmaceutical therapies aimed to prevent further cartilage loss and joint dysfunction, there are no ideal strategies that target the pathogenesis of OA. Melatonin exhibits a variety of regulatory properties by binding to specific receptors and downstream molecules and exerts a myriad of receptor-independent actions via intracellular targets as a chondrocyte protector, an anti-inflammation modulator, and a free radical scavenger.

Dihydromyricetin suppresses cell metastasis in human osteosarcoma through SP-1- and NF-κB-modulated urokinase plasminogen activator inhibition.

Background: Metastasis caused a decline in the 5-years survival rate of osteosarcoma. Therefore, developing new targeted therapeutics for osteosarcoma treatment is imperative. Dihydromyricetin (DHM) has several physiological functions: it counteracts inflammation, oxidation, and antitumor properties.

Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK-ERK Pathway.

Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells.

GO-Y078, a Curcumin Analog, Induces Both Apoptotic Pathways in Human Osteosarcoma Cells via Activation of JNK and p38 Signaling.

Osteosarcoma is the most common primary bone malignancy in teenagers and continues to confer a generally poor prognosis due to its highly metastatic potential. Poor solubility in water and instability of curcumin limits its bioavailability for use in the adjuvant situation to improve the prognosis and the long-term survival of patients with osteosarcoma. To further obtain information regarding the apoptosis induced by a new curcumin analog, GO-Y078, in human osteosarcoma cells, flow cytometric analysis, annexin V-FITC/PI apoptosis staining assay, human apoptosis array, and Western blotting were employed.

Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis.

Timosaponin AIII (TSAIII) is a steroidal saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal F-actin and cytoskeletal-related proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis.

Curcumin Analogue L48H37 Suppresses Human Osteosarcoma U2OS and MG-63 Cells' Migration and Invasion in Culture by Inhibition of uPA via the JAK/STAT Signaling Pathway.

Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, we investigated whether L48H37 represses human osteosarcoma cells' biological behavior of migratory potential and invasive activities and attempted to delve into its underlying mechanisms. L48H37 up to 5 μM inhibited, without cytotoxicity, the motility, migration, and invasion of human osteosarcoma U2OS and MG-63 cells.

New insights into molecular and cellular mechanisms of zoledronate in human osteosarcoma.

Osteosarcoma is the most common primary malignant tumor of the skeleton in teenagers and young adults and continues to confer a generally poor prognosis in patients who do not respond to chemotherapy or who present with metastatic diseases at diagnosis. The nitrogen-containing zoledronate, the third generation bisphosphonate (BP), effectively inhibits osteoclastic bone resorption and is widely utilized in the treatment of metabolic and metastatic bone diseases nowadays. Owing to an acceptable safety profile and tolerability, zoledronate is the only BP currently approved for the prevention and treatment of skeletal relevant events in patients with metastatic bone lesions, especially bone metastases from advanced renal cell carcinoma and prostate cancer, and breast cancer, due to all solid malignancy.

New insights into antimetastatic signaling pathways of melatonin in skeletomuscular sarcoma of childhood and adolescence.

Melatonin is an indole produced by the pineal gland at night under normal light or dark conditions, and its levels, which are higher in children than in adults, begin to decrease prior to the onset of puberty and continue to decline thereafter. Apart from circadian regulatory actions, melatonin has significant apoptotic, angiogenic, oncostatic, and antiproliferative effects on various cancer cells. Particularly, the ability of melatonin to inhibit skeletomuscular sarcoma, which most commonly affects children, teenagers, and young adults, is substantial.

Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf-MEK-ERK Pathway.

Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway.

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma.

Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11-15 years. Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes.

Licochalcone A-Induced Apoptosis Through the Activation of p38MAPK Pathway Mediated Mitochondrial Pathways of Apoptosis in Human Osteosarcoma Cells In Vitro and In Vivo.

Background: Licochalcone A (LicA) is isolated from the roots of and possesses antitumor and anti-invasive activities against several tumor cells. However, the antitumor effects of LicA on human osteosarcoma cells have yet to be demonstrated either in vitro or in vivo.

Methods: Cell viability was measured by MTT assay.

CLEFMA Activates the Extrinsic and Intrinsic Apoptotic Processes through JNK1/2 and p38 Pathways in Human Osteosarcoma Cells.

Due to the poor prognosis of metastatic osteosarcoma, chemotherapy is usually employed in the adjuvant situation to improve the prognosis and the chances of long-term survival. 4-[3,5-Bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid (CLEFMA) is a synthetic analog of curcumin and possesses anti-inflammatory and anticancer properties. To further obtain information regarding the apoptotic pathway induced by CLEFMA in osteosarcoma cells, microculture tetrazolium assay, annexin V-FITC/PI apoptosis staining assay, human apoptosis array, and Western blotting were employed.

Gout as a Risk Factor for Dry Eye Disease: A Population-Based Cohort Study.

This study evaluated the effect of gout on the risk of dry eye disease (DED) by using the National Health Insurance Research Database (NHIRD). Data for 30,192 gout patients (21,081 men and 9111 women) and 30,192 non-gout patients (21,005 men and 9187 women) were analyzed. Approximately 1 million patients were randomly sampled from the NHIRD registry.

Melatonin attenuates osteosarcoma cell invasion by suppression of C-C motif chemokine ligand 24 through inhibition of the c-Jun N-terminal kinase pathway.

Osteosarcoma, with its high metastatic potential, is the most prevalent malignant bone tumor in children and adolescents. Melatonin possesses multiple tumor-suppressing properties for a myriad of tumors, but little is known about the effects of melatonin on osteosarcoma metastasis. In this study, we demonstrated that melatonin elicited very low cytotoxicity and significantly inhibited cellular motility, migration, and invasion in human osteosarcoma U2OS and HOS cells.

Tricetin inhibits human osteosarcoma cells metastasis by transcriptionally repressing MMP-9 via p38 and Akt pathways.

Tricetin, a dietary flavonoid, has cytostatic properties and anti-metastasis activities in various cancer cells. However, the detailed impacts and underlying mechanisms of tricetin on human osteosarcoma cell metastasis are still unclear. Here, the hypothesis that tricetin possesses the anti-metastatic effects on human osteosarcoma cells was tested.

3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo.

Many natural flavonoids have cytostatic and apoptotic properties; however, we little know whether the effect of synthetic 3-hydroxyflavone on metastasis and tumor growth of human osteosarcoma. Here, we tested the hypothesis that 3-hydroxyflavone suppresses human osteosarcoma cells metastasis and tumor growth. 3-hydroxyflavone, up to 50 μM without cytotoxicity, inhibited U2OS and 143B cells motility, invasiveness and migration by reducing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and also impaired cell adhesion to gelatin.

Arthroscopic Lateral Retinacular Release and Modified Elmslie-Trillat Operation Improve Severe Isolated Lateral Patello-Femoral Osteoarthritis.

To evaluate whether arthroscopic lateral retinacular release and the modified Elmslie-Trillat operation improve osteoarthritis (OA) progression and clinical outcomes in patients with severe isolated lateral patello-femoral OA. Nine women (11 knees) and one man (one knee) with isolated late-stage lateral patello-femoral OA underwent surgery. The severity of patello-femoral OA was recorded using the Merchant method, while the level of pain and anterior knee function were scored using the visual analogue scale (VAS) and Kujala knee scores, respectively.

Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression.

Nobiletin, a polymethoxyflavone, has a few pharmacological activities, including anti-inflammation and anti-cancer effects. However, its effect on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of nobiletin against cellular metastasis of human osteosarcoma and the underlying mechanisms.