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Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.

Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Herein, we systematically investigated the effects of FUR on the significant processes of tumor progression with the relatively low concentrations in 95-D lung cancer cells. FUR concentration-dependently inhibited cell proliferation and blocked the cell cycle progressions in G1 phase by down-regulating the protein levels of cyclin D1 and CDK6, and up-regulating those of p21 and p27 in 95-D cells. FUR also affected the signaling molecules that regulate apoptosis in 95-D cells revealed by the down-regulation of the protein levels of full PARP, pro-caspase-7, survivin, and Bcl-2, and the up-regulation of cleaved PARP. Further studies showed that FUR enhanced the expression of light chain 3-II (LC3-II) in the protein level, indicating that autophagy is involved in this process. Besides, the adhesion ability of 95-D cells to matrigel and fibronectin was slightly inhibited after FUR treatment for 1 h in our experimental condition. FUR also slightly suppressed cell migration and invasion in 95-D cells according to the data from wound healing and Transwell assays, respectively. Taken together, FUR activated the signal molecules regulating G1 cell cycle arrest, apoptosis and autophagy, while slightly affecting the key steps of cell metastasis in 95-D lung cancer cells in the relatively low concentrations.

Melanoma cell metastasis is the primary cause of patient death. Thus, various treatment strategies have been developed to prevent metastasis. Abietic acid (AA) is an organic compound commonly found in trees. This study is aimed to investigate the antimetastatic activity of AA in B16F10-xenografted C57BL/6 mice and assess the anticancer activity of AA in combination with Taxol in melanoma cells. AA effectively reduced the formation of lung metastases by approximately 92.8%. AA treatment inhibited migratory potential ($p<0.001$), invasion ($p<0.001$), and motility ($p<0.001$) of highly metastatic B16F10 melanoma cells in vitro. Zymography revealed that AA reduced the proteinase activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Molecular analyses showed that AA reduced Akt phosphorylation and activating protein-1 DNA-binding activity by Western blot and electrophoretic mobility shift assay (EMSA), respectively. In summary, AA effectively inhibited B16F10 lung metastasis, and 50$\mu$M AA did not affect the viability of B16F10 cells. AA improved the efficacy of Taxol and demonstrated strong anticancer activity on melanoma cells. These results suggested that AA could be used as an antimetastatic agent or as an adjuvant for anticancer therapy.

Although Arctii Fructus (AF) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of AF on the metastatic properties of colorectal cancer (CRC). The aim of this study was to investigate whether AF could suppress CRC progression by inhibiting cell growth, epithelial-mesenchymal transition (EMT), migration, and the invasion ability of CRC cells. AF decreased proliferation of CRC cells by inducing cell cycle arrest and apoptosis via extrinsic and intrinsic apoptotic pathways. Regarding metastatic properties, AF inhibited EMT by increasing the expression of the epithelial marker, E-cadherin, and decreasing the expression of the mesenchymal marker, N-cadherin, in CT26 cells. Moreover, AF decreased the migration and invasion of CT26 cells by inhibiting matrix metalloproteinase-2 (MMP-2) and MMP-9 activity. We confirmed that the decreased invasion ability and MMP-9 activity by AF treatment involved AMP-activated protein kinase (AMPK) activation. Collectively, this study demonstrates that AF inhibits the proliferation and metastatic properties of CRC cells.

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

Metastasis is the most prevalent cause of cancer-associated deaths amongst patients with cervical cancer. Epithelial–mesenchymal transition (EMT) is essential for carcinogenesis, and it confers metastatic properties to cancer cells. Gossypol is a natural polyphenolic compound with anti-inflammation, anti-oxidant, and anticancer activities. In this study, we investigated the antimetastatic and antitumour effects of gossypol on human cervical cancer cells (HeLa and SiHa cells). Gossypol exerted a strong inhibition effect on the migration and invasion of human cervical cancer cells. It reduced the focal adhesion kinase (FAK) pathway-mediated expression of matrix metalloproteinase-2 and urokinase-type plasminogen activator, subsequently inhibiting the invasion of SiHa cells. In addition, gossypol reversed EMT induced by transforming growth factor beta 1 (TGF-$\beta$1) and up-regulated epithelial markers, such as E-cadherin but significantly suppressed Ras homolog family member (Rho)A, RhoB, and p-Samd3. The tail vein injection model showed that gossypol treatment via oral gavage reduced lung metastasis. Gossypol also decreased tumour growth in vivo in the nude mouse xenograft model. All these findings suggest that gossypol suppressed the invasion and migration of human cervical cancer cells by targeting the FAK signaling pathway and reversing TGF-$\beta$1-induced EMT. Hence, gossypol warrants further attention for basic mechanistic studies and drug development.

Invasion and metastasis are the major causes leading to the high mortality of colon cancer. Ginsenoside Rg3 (Rg3), as a bioactive ginseng compound, is suggested to possess antimetastasis effects in colon cancer. However, the underlying molecular mechanisms remain unclear. In this study, we reported that Rg3 could effectively inhibit colon cancer cell invasion and metastasis through in vivo and in vitro studies. In addition, Rg3 suppressed the epithelial–mesenchymal transition (EMT) of HCT15 cells and SW48 cells evidenced by detecting EMT related markers E-cadherin, vimentin, and snail expression. Furthermore, inhibition of Notch signaling by LY411,575 or specific Hes1 siRNA obviously repressed colon cancer cell migration and metastasis, and induced increase in E-cadherin and decrease in vimentin and snail. Meanwhile, the expression of NICD and Hes1 was obviously decreased in the presence of Rg3. However, Rg3 failed to suppress EMT in Hes1 overexpressed colon cancer cells. In particular, Rg3 significantly reversed IL-6-induced EMT promotion and blocked IL-6- induced NICD and Hes1 upregulations. Overall, these findings suggested that Rg3 could inhibit colon cancer migration and metastasis via suppressing Notch-Hes1-EMT signaling.

Mistletoe extracts (Viscum album L.) have been widely used as complementary and alternative medicines for the treatment of cancer, and their cytotoxic effects have been reported on various types of cancer. However, the molecular targets of mistletoe extracts have not been well studied. Herein, we investigated molecules associated with the in vitro and in vivo anticancer effects of mistletoe extract using 4T1 murine breast cancer cells. Mistletoe extract induced apoptosis and inhibited the signal transducer and activator of transcription3 (STAT3) phosphorylation. This inhibition was accompanied by the downregulations of forkhead box M1 (FOXM1) and the DNA repair proteins, RAD51 and survivin. Mistletoe extract simultaneously increased the expression of the DNA damage marker proteins, phosphorylated H2A histone family member X (H2A.X), and phosphorylated p38. Furthermore, mistletoe extract effectively suppressed tumor growth in 4T1 tumor-bearing BALB/c mice. In addition to tumor growth inhibition, mistletoe extract inhibited lung metastasis in the tumor-bearing mice and cell invasiveness by downregulating the expressions of matrix metalloproteinases (MMPs), urokinase-type plasminogen activator (uPA), uPA receptor, and markers of epithelial-mesenchymal transition (snail and fibronectin). Taken together, our results suggest that mistletoe extract targets the STAT3-FOXM1 pathway for its cytotoxic effects, and that mistletoe extracts might be useful for the treatment of patients with cancers highly expressing the STAT3-FOXM1 pathway.

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75–30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

Human oral squamous cell carcinomas (OSCCs) have high cancer mortality and a 5-year survival rate lower than that of most other carcinomas. New therapeutic strategies are required for the treatment and prevention against OSCCs. An approach to cancer therapy using plant-derived natural compounds has been actively in progress as a trend. Falcarindiol (FALC), or its isolated form Ostericum koreanum Kitagawa (O. koreanum), is present in many food and dietary plants, especially in carrots, and this compound has a variety of beneficial effects. However, biological activity of FALC has not been reported in OSCCs yet. This study aimed to demonstrate the antitumor effects of FALC against OSCCs, YD-10B cells. In this study, FALC was selected as a result of screening for compounds isolated from various natural products in YD-10B cells. FALC suppressed cell growth, and FALC-induced apoptotic cell death was mainly accompanied by the dephosphorylation of PI3K, AKT, mTOR, and p70S6K. The apoptotic cell death was also associated with autophagy as evidenced by the expression of Beclin-1, the conversion of LC3-II, and the formation of autophagosome. FALC-induced autophagy was accompanied by MAPKs including ERK1/2 and p38. Furthermore, FALC caused the antimetastatic effects by inhibiting the migration and invasion of YD-10B cells. Taken together, the findings suggest the potential value of FALC as a novel candidate for therapeutic strategy against OSCCs.

18$\beta$-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-$\beta$ (TGF-$\beta )$-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-$\beta$-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-$\beta$. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-$\beta$-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-$\beta$-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-$\beta$-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

Breast cancer is one of the most common malignancies in women, and exhibits high metastasis, recurrence and fatality rates. Novel therapies for breast cancer are constantly emerging, such as targeted therapy, oncolytic virotherapy, and immunotherapy. Despite their potential, these new therapies are still in their infancy, and chemotherapy remains the standard treatment for breast cancer. Therefore, it is of great significance to develop safe and efficient treatment drugs or adjuvants for breast cancer treatment. Traditional Chinese medicine (TCM) has a long clinical history in China, in which Scutellaria baicalensis Georgi exhibits favorable antibreast cancer activities. We therefore conducted a systematic review of the available literature to better understand the molecular mechanisms of S. baicalensis in breast cancer treatment. S. baicalensis and its active components (baicalein, baicalin, wogonin, wogonoside, oroxylin A and scutellarin) exhibited promising antibreast cancer activity through proliferation inhibition, apoptosis induction, invasion and metastasis blockading, and drug-resistance and non-coding RNA regulation. Additionally, senescence, autophagy, angiogenesis, and glycolysis mechanisms were observed to play a role in their antibreast cancer activity. Furthermore, multiple signaling pathways contributed to the antitumor effects of S. baicalensi, such as the NF-$\kappa$B, Wnt/$\beta$-catenin, SATB1, Bcl2 family proteins, Caspase, PI3K/Akt, mTOR, ERK, p38-MAPK, TGF-$\beta$/Smad, and Hippo/YAP pathways. This review provides valuable insights into the role of S. baicalensis as a breast cancer treatment and acts as a foundation for further investigations in this field.

Metastasis of osteosarcoma is an important adverse factor affecting patients’ survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100$\mu$M, 24h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment’s inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin’s dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

The goal of this paper is to solve mathematical model equations on solid tumour growth and compute their parameter values by applying growth rates of prostate cancer cell lines in vivo. For these computations, we investigate previously developed C3(1)/Tag transgenic models of prostate cancer. To make the computations fast, we have constructed an algorithm, which is based on small amounts of spatial grid-points and obtained a correspondence between the in vivo growth of tumours and the solutions of the model equations.

Pathological lesions of long bones increase the morbidity of many common cancers. The orthopedic management of metastatic skeletal lesions can be challenging. The ultimate aim is to provide patients with a painless, functional limb. We present a report of two cases were a novel minimally invasive long bone nailing technique has been utilized to achieve skeletal stability and alleviation of symptoms.

Hepatocellular carcinoma (HCC) is a common cancer with a high rate of metastasis to sites, such as, lung, bone, and regional lymph nodes. However, metastasis of HCC to the hand is rare and the majority of reported cases involve hand bones. Here, the authors report a rare case of finger skin metastasis from HCC without bone involvement. This case highlights that patients presenting with a nodule or granuloma-like tumor of the hand should generate a suspicion of metastasis when there is a history of HCC.

It is well known that the coagulation factor XIII (FXIII) is deeply involved in wound healing and tissue regeneration. We measured the plasma levels of FXIII (FXIII levels) before and after surgery in 80 patients with bone tumors [benign tumors in 30 patients (BT group), malignant tumors in 30 patients (MT group), and carcinoma metastasis in 20 patients (CM group)] and in the control group which consisted of 30 patients with osteoarthritis of the hip joint who had underwent total hip arthroplasty (THA). The numbers of patients whose preoperative FXIII level was below the lower limit of normal were as follows: 0 (0%) among 30 patients in the control group; 7 (23%) among 30 patients in the BT group; 12 (40%) among 30 patients in the MT group; and 9 (45%) among 20 patients in the CM group. Among patients with bone tumors examined in this study, patients with osteosarcoma who underwent chemotherapy showed a significant decrease in FXIII levels (p < 0.01). We indicated not only FXIII levels in patients with bone tumors, but also the natural time-course of FXIII levels in patients who underwent orthpaedic surgery of THA at the first time.

Exploring the Role of Glutathione in the Regulation of Immune Cell Function.

Does Oxidative Damage Cause Poor Healing?

Pathogenesis of Atopic Dermatitis in Singapore.

Proteomics and Colorectal Cancer Metastasis: Bird's-Eye View on Current Scenario and Our Contribution.

Zebrafish: A Small Fish Model for a Big Human Disease.

The Reign of a New Dictator: Circulating MicroRNA in Diabetes.

Engineering Artificial Vascularized Bone Grafts for the Repair of Large Bone Defects.

A 'Nano' Era for Blood Glucose Sensing.

Ancient Medicine with Newer Roles: Potential Role of Celastrol in the Treatment of Multiple Myeloma.

Proteins, Proteome and Proteomics.

A Novel Promising Biomarker and Therapy Target of Liver Cancer.

INDIA – Ozone eating away Indian crop yields.

INDIA – Polio shots better than oral drops, says study.

JAPAN – Natural protein in rice helps keep arsenic out in grains.

THE PHILIPPINES – Philippines adopts inactivated polio vaccine strategy.

SINGAPORE – A*STAR's Institute of Microelectronics and Singapore Biomicro to develop a first-of-its-kind, implantable wireless blood glucose monitoring sensor device.

THAILAND – Ebola-affected countries face new threat: food crisis.

THAILAND – Fending off dengue with insecticide-treated uniforms.

AFRICA – New test to combat major cause of preventable blindness in Africa.

BANGLADESH – Arsenic linked to lung cancer in Bangladesh.

EUROPE – Human-milk-oligosaccharides can protect against noroviruses.

UNITED STATES – Researchers discover possible cause of common dementia.

UNITED STATES – Improved mouse model may accelerate research on potential Ebola vaccines and treatments.

UNITED STATES – New device yields close-up look at metastasis.

UNITED STATES – Scientists research ways to use an organism's own pathway to synthesize potential therapeutics.

RESEARCH HIGHLIGHTS – Quality issues in herbal medicine clinical trials.

INDIA – Stem cell therapy is ‘no remedy for stroke’.

THE PHILIPPINES – Farmers losing from GM eggplant ban, says expert.

SINGAPORE – Breakthrough discovery by researchers contributes towards future treatment of multiple sclerosis and autoimmune inflammation.

VIETNAM – Some Asians found to carry gene resistant to typhoid.

VIETNAM – Vietnam eyes water-saving technology for its rice farms.

AFRICA – South Africa's healthcare ‘still burdened with diseases’.

AFRICA – Healthcare workers use buddy system to fight Ebola.

AFRICA – STI ministerial summit appeals for Africa-led research.

BANGLADESH – Jute as possible arsenic remover in Bangladesh.

EGYPT – Interest grows in unusual Egyptian method of mosquito control.

EUROPE – Research team proves the efficacy of new drug against stem cells that provoke the onset and growth of cancer and its metastasis.

UNITED STATES – Protein predicts response to new immunotherapy drug.

UNITED STATES – A link between DNA transcription and disease causing expansions which lead to hereditary disorders.

UNITED STATES – Penn Medicine team develops cognitive test battery to assess the impact of long duration spaceflights on astronauts' brain function.

UNITED STATES – Survival differences seen for advanced-stage laryngeal cancer.

UNITED STATES – Mosquitoes and malaria: Scientists pinpoint how biting cousins have grown apart.