4 research outputs found
Anti-tumor Activity of NuvastaticTM (C5OSEW5050ESA) of Orthosiphon stamineus and Rosmarinic Acid in An Athymic Nude Mice Model of Breast Cancer
The current treatment strategies for metastatic breast cancer depend on the cancer subtype by palliating symptoms and prolonging life. However, triple-negative breast cancers have no targeted treatment available. Orthosiphon stamineus (O.s) is a traditional folk medicine plant used in South East Asia to treat many diseases. The aim of this study is to evaluate the anti-tumor activity of O.s extract formulation (ID: C5EOSEW5050ESA trademarked as NuvastaticTM) and its major component, rosmarinic acid in a breast in vivo tumor xenograft model. Human triple-negative breast cancer cells were transplanted into the mammary fat pad of 20 athymic nude mice. Fourteen days post-injection, mice were randomly assigned to four groups. C5EOSEW5050ESA (200 and 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally. The body weight and tumor size were measured twice a week. Histopathological analyses of tumor tissues were conducted. Tumor necrosis and tumor growth were determined by hematoxylin and eosin staining. A significant reduction in tumor size and growth was found in all treatment groups. No significant difference between C5EOSEW5050ESA at 200 mg/kg and rosmarinic acid in the reduction of tumor size and necrosis. However, a more significant reduction was found in tumor growth and necrosis with 400 mg/kg of C5EOSEW5050ESA treatment as compared to other treatments. These results highlighted the anti-tumor activity of C5EOSEW5050ESA in reducing breast tumor growth in mice compared to the lower dose of C5EOSEW5050ESA and rosmarinic acid. This study provides valuable insights into using C5EOSEW5050ESA as a treatment to target triple-negative breast cancers in vivo
Recommended from our members
Experimental models of gut‐first Parkinson's disease: A systematic review
BackgroundThere is strong support from studies in humans and in animal models that Parkinson's disease (PD) may begin in the gut. This brings about a unique opportunity for researchers in the field of neurogastroenterology to contribute to advancing the field and making contributions that could lead to the ability to diagnose and treat PD in the premotor stages. Lack of familiarity with some of the aspects of the experimental approaches used in these studies may present a barrier for neurogastroenterology researchers to enter the field. Much remains to be understood about intestinal-specific components of gut-first PD pathogenesis and the field would benefit from contributions of enteric and central nervous system neuroscientists.PurposeTo address these issues, we have conducted a systematic review of the two most frequently used experimental models of gut-first PD: transneuronal propagation of α-synuclein preformed fibrils and oral exposure to environmental toxins. We have reviewed the details of these studies and present methodological considerations for the use of these models. Our aim is that this review will serve as a framework and useful reference for neuroscientists, gastroenterologists, and neurologists interested in applying their expertise to advancing our understanding of gut-first PD
Recommended from our members
BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis.
BackgroundThe development of new vasculatures (angiogenesis) is indispensable in supplying oxygen and nutrients to fuel tumor growth. Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer (CRC) progression. Sirtuin (SIRT) enzymes are highly expressed in blood vessels. BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC. However, its role has yet to be explored in CRC tumor angiogenesis.AimTo investigate the anti-angiogenic potential of BZD9L1 on endothelial cells (EC) in vitro, ex vivo and in HCT116 CRC xenograft in vivo models.MethodsEA.hy926 EC were treated with half inhibitory concentration (IC50) (2.5 μM), IC50 (5.0 μM), and double IC50 (10.0 μM) of BZD9L1 and assessed for cell proliferation, adhesion and SIRT 1 and 2 protein expression. Next, 2.5 μM and 5.0 μM of BZD9L1 were employed in downstream in vitro assays, including cell cycle, cell death and sprouting in EC. The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction (qPCR). The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array. Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC. The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids. HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis, Ki67 protein expression indicative of proliferation, cluster of differentiation 31 (CD31) and CD34 EC markers, and SIRT 1 and 2 genes via hematoxylin and eosin, immunohistochemistry and qPCR, respectively.ResultsBZD9L1 impeded EC proliferation, adhesion, and spheroid sprouting through the downregulation of intercellular adhesion molecule 1, vascular endothelial cadherin, integrin-alpha V, SIRT1 and SIRT2 genes. The compound also arrested the cells at G1 phase and induced apoptosis in the EC. In mouse choroids, BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control. Compared to the negative control, the compound also reduced the protein levels of angiogenin, basic fibroblast growth factor, platelet-derived growth factor and placental growth factor, which then inhibited HCT116 CRC spheroid invasion in co-culture. In addition, a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1 (hSIRT1), hSIRT2, CD31, and CD34 EC markers and murine SIRT2 gene, while the murine SIRT1 gene remained unaffected, compared to vehicle control. Histology analyses revealed that BZD9L1 at low (50 mg/kg) and high (250 mg/kg) doses reduced Ki-67 protein expression, while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.ConclusionThese results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression. Furthermore, together with previous anticancer findings, this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome
Recommended from our members
Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.
BackgroundEvidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression.ObjectiveTo identify early molecular changes in the gut-brain axis in Thy1-haSyn mice through gene expression profiling.MethodsGene expression profiling was performed on gut (colon) and brain (striatal) tissue from Thy1-haSyn and wild-type (WT) mice aged 1 and 3 months using 3' RNA sequencing. Analysis included differential expression, gene set enrichment and weighted gene co-expression network analysis (WGCNA).ResultsAt one month, differential expression (Thy1-haSyn vs. WT) of mitochondrial genes and pathways related to PD was discordant between gut and brain, with negative enrichment in brain (enriched in WT) but positive enrichment in gut. Linear regression of WGCNA modules showed partial independence of gut and brain gene expression changes. Thy1-haSyn-associated WGCNA modules in the gut were enriched for PD risk genes and PD-relevant pathways including inflammation, autophagy, and oxidative stress. Changes in gene expression were modest at 3 months.ConclusionsOverexpression of haSyn acutely disrupts gene expression in the colon. While changes in colon gene expression are highly related to known PD-relevant mechanisms, they are distinct from brain changes, and in some cases, opposite in direction. These findings are in line with the emerging view of PD as a multi-system disease