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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,063 records · Page 59
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Synthesis of novel α-aminophosphonates under microwave irradiation, biological evaluation as antiproliferative agents and apoptosis inducers

The synthesis of two series of α-aminophosphonates was achieved by Microwave Irradiation (MW), using the one-pot Kabachnik–Fields reaction. Based on a green chemistry approach, the reactions were carried out using ethanol as the only solvent and without any catalyst, and short reaction times (20–40 min), in variable yields. Both series were tested to determine their cell proliferation inhibition activity in MDA-MB-231, MCF-7 and MCF-10A cell lines. Ethyl 4-(((diphenoxyphosphoryl)(4-(diphenylamino)phenyl)methyl)amino) benzoate 4e and diphenyl (((4-(((S)-2-hydroxy-1-phenylethyl)carbamoyl)phenyl)amino)(4-hydroxyphenyl)methyl)phosphonate 6b, showed cell proliferation inhibition activity only in the cancer cell line MCF-7 and no effect on the normal cell line MFC-10A, both compounds caused cell death by inducing apoptosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Screening for anticancer properties of thiazolidinedione compounds in a galactose media metastatic breast cancer cell model

The metastatic tumors of breast cancer lead to the mortality of patients in part due to the failure of chemotherapeutics to reach the brain and emergence of drug resistance. With the increase in drug resistance, we focused on targeting mitochondrial metabolism, which was recently found to be a viable and novel drug target in breast cancer. Here we screened several ligands for anticancer activity in a phenotypic screen using the MTT dye as a marker for cell proliferation. MCF-7 breast cancer cells were treated with compounds in the presence of galactose to ensure mitochondrial interaction by the compounds. The lead compound of our group, NL-1, a thiazolidinedione (TZD), was found to inhibit cell proliferation with an IC{sub 50} of 7.1 μM, whereas its unsaturated derivative CI-987 was more potent with a IC{sub 50} of 3.3 μM. The TZDs were affected by substitution on both the aromatic ring and the TZD warhead. Taken together, these compounds can serve as lead structures for mitochondrial targeted drug discovery programs in breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Effect of Polyethylene Terephthalate on Functional Properties of Endothelial and Mesenchymal Cells

We studied the influence of vascular prostheses made of polytetrafluoroethylene and polyethylene terephthalate on the proliferation, migration, and NO production by bone marrow mesenchymal stem cells, human endothelial progenitor cells, and EA.hy926 endothelial cells, colonization of the prosthesis surface by endothelial and mesenchymal cells was also analyzed. Synthetic prostheses have a negative effect on cell proliferation and migration, while surface treatment with proteins (fibronectin or gelatin) promotes colonization of the prostheses with cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Changes in the Metastatic Properties of MDA-MB-231 Cells after IGFBP6 Gene Knockdown Is Associated with Increased Expression of miRNA Genes Controlling INSR, IGF1R, and CCND1 Genes

Metastatic cascade is associated with the process of epithelial-mesenchymal transition accompanied by changes in cell proliferation, migration, adhesion, and invasiveness mediated by the insulin-like growth factor (IGF) signal pathway. IGFBP6 protein binds IGF and prevents its interaction with receptors. IGFBP6 gene knockdown through RNA-interference inhibits cell migration and increased the rate of proliferation of breast cancer MDA-MB-231 cells. IGFBP6 knockdown cells are characterized by increased expression of MIR100 and MIRLET7A2 genes encoding hsa-miR-100-3p, hsa-miR-100-5p, hsa-let-7a-5p, and hsa-let-7a-2-3p miRNA. The target genes of these microRNAs are IGF2, IGF1R, INSR, and CCND1 associated with IGF signaling pathway and proliferative and migratory activity during the metastatic cascade. A significant decrease in the expression of INSR and CCND1 genes was demonstrated by PCR and microarray analysis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Regulation of Proliferative Processes in Rat Adrenal Cortex by Transcriptional Factor PRH under Conditions of Developmental Exposure to Endocrine Disruptor DDT

The effects of endocrine disrupters of transcriptional control of morphogenesis are poorly studied. Changes in the expression of transcriptional factor PRH and proliferation of adrenal cortical cells were analyzed in pubertal and postpubertal rats exposed prenatally and postnatally to low doses of endocrine disrupter DDT. In rats exposed to DDT, the expression of PRH and proliferation of adrenal cortical cells differed from those in control rats. Association between these parameters was weakened in the zona glomerulosa and zona reticularis and was absent in the zona fasciculata. These findings suggest that exposure to DDT in pre- and postnatal periods impairs the regulation of proliferative processes by transcriptional factor PRH in all zones of rat adrenal cortex, which can be a mechanism of the disruptive action of DDT.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Evaluation of additive manufacturing side channels for nuclear nonproliferation applications

The nuclear industry is continuing to grow and adopt new technologies to manufacture components. One of the technologies under consideration is additive manufacturing (AM). AM could make production of components at lower cost and could lessen lead times significantly. However, AM could be prone to proliferation risks. AM machines give off signatures during the manufacturing process, and these signatures offer an alternative means of observing the component. Correlations between these signatures and the geometry being manufactured could be developed; enabling proliferators as they could take advantage of these correlations to steal AM manufacturing instructions relating to nuclear technology. This work pertains to preliminary work exploring the feasibility of tapping into AM side channels to predict geometries being manufactured on AM machines. The feasibility of utilizing vibration to draw geometric correlations will be assessed on an Ultimaker 2 + thermoplastic 3D printer.

Additive manufacturing↗
DOE OSTI2019

Fabrication and Cytocompatibility Evaluation of Psyllium Husk (Isabgol)/Gelatin Composite Scaffolds

Psyllium husk or isabgol contains xylan backbone linked with arabinose, rhamnose, and galacturonic acid units (arabinoxylans). In this study, we demonstrate the fabrication and characterization of a macroporous three-dimensional (3D) composite scaffold by mixing psyllium husk powder (PH) and gelatin (G) in different ratios, viz.100 PH, 75/25 PH/G, and 50/50 PH/G (w/w), using an EDC-NHS coupling reaction followed by freeze-drying method. The reaction was performed in aqueous as well as in alcoholic media to determine the most appropriate solvent system for this purpose. The mechanical strength of the scaffold system was improved from 151 to 438 kPa. The fabricated scaffolds exhibited enhanced structural stability, remarkable swelling capacity, and escalated cell growth and proliferation. ATR-FTIR analysis showed the presence of amide and ester bonds indicating covalent crosslinking. SEM micrographs revealed the porous nature of the scaffolds with pores ranging from 30 to 150 μm, and further pore size distribution curve indicated that 75/25 PH/G (w/w%) EDC-NHS-alcohol scaffold exhibited the best fit to the Gaussian distribution. Swelling capacity of the 100 PH EDC-NHS-alcohol scaffolds was found to be nearly 40% from its original weight in 48 h. MTT assay using fibroblast cells revealed ~ 80% cellular proliferation by 6th day within the fabricated scaffolds in comparison to control. .

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

IL-39 acts as a friend to pancreatic cancer

Pancreatic cancer is the most lethal digestive cancer and the fourth leading cause of cancer death in the US. IL-39, a heterodimer of p19 and EBI3, is a newly found cytokine and its role in the pathogenesis of neoplasia has not been studied yet. This study was designed to investigate the direct role of IL-39 in the growth of pancreatic cancer. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the direct effects of IL-39 on cell survival, proliferation and apoptosis of the widely studied pancreatic cancer cell line MiaPaCa-2. We further investigated the possible molecular mechanisms by using RT-PCR and IHC. The percentage of colonies of pancreatic cancer cells increased significantly in the presence of IL-39. This was paralleled with the increase in the OD value of cancer cells in the presence of IL-39. Interestingly, the relative caspase-3 activity in cancer cells decreased significantly in the presence of IL-39. Furthermore, the pro-tumor effect of IL-39 on pancreatic cancer cells correlated with decreased anti-proliferative molecule p21.The anti-apoptotic effect of IL-39 correlated with decreased pro-apoptotic molecule TRAILR1. These results suggest that IL-39 favors growth of pancreatic cancer by promoting growth and inhibiting apoptosis of cancer cells. This suggests that IL-39 acts as a friend to pancreatic cancer. Thus, inhibition of effect of IL-39 on cells might be a promising strategy to treat pancreatic cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Identification of candidate diagnostic and prognostic biomarkers for human prostate cancer: RPL22L1 and RPS21

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. This study was designed to investigate the potential of Ribosomal Protein L22-like1 (RPL22L1) and Ribosomal Protein S21 (RPS21) as diagnostic and prognostic biomarkers for PCa. First, RPL22L1 and RPS21 were screened as the key molecular of PCa by bioinformatics analysis. Subsequently, the prostate tissue samples were stained for antibodies against RPL22L1 and RPS21. The unbiased signal quantification was performed by ImageJ software, and the results showed that the expression of RPL22L1 and RPS21 exhibited significant differences between the PCa tissues and the normal prostate tissues. Receiver-operating characteristics (ROC) curves were prepared, and then the area under the curve (AUC) values of RPL22L1 and RPS21 were calculated as 0.798 and 0.768, and the likelihood ratio (LR) values of RPL22L1 and RPS21 were calculated as 2.86 and 2.53. These data implied that the over-expression of RPL22L1 and RPS21 is associated with the presence of PCa. The further analysis suggested that the expression of RPL22L1 and RPS21 were significantly higher in high Gleason grade than they were in low Gleason grade. In addition, in vitro studies were undertaken to evaluate the roles of RPL22L1 and RPS21 in PCa. The results revealed that these genes promote PCa cell proliferation, migration and invasion, and inhibit PCa cell apoptosis. Taken together, these data showed that RPL22L1 and RPS21 exhibited higher expression in human prostate cancer tissue, and involved in PCa cell proliferation and invasion. This research provided a novel insight into diagnostic and prognostic biomarkers for PCa.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Proteoglycan from salmon nasal cartridge promotes in vitro wound healing of fibroblast monolayers via the CD44 receptor

Highlights: • Proteoglycan from salmon nasal cartridge (SNC-PG) promoted wound healing in fibroblast monolayers. • SNC-PG stimulated both cell proliferation and cell migration. • Interaction between chondroitin sulfate-units and CD44 is responsible for the effect. - Abstract: Proteoglycans (PGs) are involved in various cellular functions including cell growth, adhesion, and differentiation; however, their physiological roles are not fully understood. In this study, we examined the effect of PG purified from salmon nasal cartilage (SNC-PG) on wound closure using tissue-cultured cell monolayers, an in vitro wound-healing assay. The results indicated that SNC-PG significantly promoted wound closure in NIH/3T3 cell monolayers by stimulating both cell proliferation and cell migration. SNC-PG was effective in concentrations from 0.1 to 10 μg/ml, but showed much less effect at higher concentrations (100–1000 μg/ml). The effect of SNC-PG was abolished by chondroitinase ABC, indicating that chondroitin sulfates (CSs), a major component of glycosaminoglycans (GAGs) in SNC-PG, are crucial for the SNC-PG effect. Furthermore, chondroitin 6-sulfate (C-6-S), a major CS of SNC-PG GAGs, could partially reproduce the SNC-PG effect and partially inhibit the binding of SNC-PG to cells, suggesting that SNC-PG exerts its effect through an interaction between the GAGs in SNC-PG and the cell surface. Neutralization by anti-CD44 antibodies or CD44 knockdown abolished SNC-PG binding to the cells and the SNC-PG effect on wound closure. These results suggest that interactions between CS-rich GAG-chains of SNC-PG and CD44 on the cell surface are responsible for the SNC-PG effect on wound closure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression

Highlights: • The number of secondary hair follicles is reduced by half in Trps1 KO embryonic skin compared to wild-type skin. • Noggin expression is significantly decreased and BMP signaling is promoted in Trps1 KO embryonic skin. • Treatment with a Noggin or BMP inhibitor rescued the decreased number of hair follicles in Trps1 KO skin graft cultures. • Cell proliferation and apoptosis of the epidermis were normalized by Noggin treatment. - Abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient’s hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model{sub ,} PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention

Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS. - Highlights: • Fenofibrate treatment improved pathological changes in thoracic aorta by chronic high-fat-diet feeding. • Fenofibrate pretreatment improved endothelium-dependent vasodilation impaired by different concentrations of palmitic acid. • The inhibition of proliferation in endothelial cells by palmitic acid were inverted by fenofibric acid. • Phosphorylation of eNOS and expression of ER stress related genes were inverted by fenofibrate or fenofibric acid.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Inhibition of H3K9 methyltransferase G9a induces autophagy and apoptosis in oral squamous cell carcinoma

Objective: To explore whether inhibition of H3K9 Methyltransferase G9a could exert an antitumoral effect in oral squamous cell carcinoma (OSCC). Materials and methods: First we checked G9a expression in two OSCC cell lines Tca8113 and KB. Next we used a special G9a inhibitor BIX01294 (BIX) to explore the effect of inhibition of G9a on OSCC in vitro. Cell growth was tested by typlan blue staining, MTT assay and Brdu immunofluorescence staining. Cell autophagy was examined by monodansylcadaverine (MDC) staining, LC3-II immunofluorescence staining and LC3-II western blot assay. Cell apoptosis was checked by FITC Annexin-V and PI labeling, tunnel staining and caspase 3 western blot assay. Finally, the effect of inhibition of G9a on clonogenesis and tumorigenesis capacity of OSCC was analyzed by soft agar growth and xenograft model. Results: Here we showed that G9a was expressed in both Tca8113 and KB cells. Inhibition of G9a using BIX significantly reduced cell growth and proliferation in Tca8113 and KB. Inhibition of G9a induced cell autophagy with conversion of LC3-I to LC3-II and cell apoptosis with the expression of cleaved caspase 3. We also found that inhibition of G9a reduced colony formation in soft agar and repressed tumor growth in mouse xenograph model. Conclusion: Our results suggested that G9a might be a potential epigenetic target for OSCC treatment. - Highlights: • Inhibition of G9a reduced cell growth and proliferation in OSCC cells. • Inhibition of G9a induces autophagy and apoptosis in OSCC cells. • Inhibition of G9a repressed tumor growth in mouse xenograph model.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited cell proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells

We demonstrate that chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, has an anticancer activity. We investigate its molecular mechanism in depth in HCT116 cells. CME reduces the amount of β-catenin in nucleus and inhibits the binding of β-catenin to specific DNA sequences (TCF binding elements, TBE) in target gene promoters. Thus, CME appears to decrease the expression of cell cycle regulatory proteins such as Cyclin D1, as a representative target for β-catenin, as well as CDK2 and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase. Therefore, we suggest that CME as a novel Wnt/β-catenin inhibitor can be a putative agent for the treatment of colorectal cancers. - Highlights: • CME inhibits cell proliferation in HCT116 cells. • CME increases cell cycle arrest at G0/G1 phase and apoptosis. • CME attenuates cyclin D1 and regulates cell cycle regulatory proteins. • CME inhibits β-catenin translocation to nucleus.

60 APPLIED LIFE SCIENCES↗