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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 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Synthesis of dehydro-α-lapachones, α- and β-lapachones, and screening against cancer cell lines

14 new naphthoquinones were prepared and tested against human cancer cell lines PC-3 (prostate), HCT-116 (colon carcinoma), SNB-19 (glioblastoma), HL-60 (leukemia) and MCF-7 (breast), and a nontumor cell line L929 (murine fibroblasts) to determine cytotoxicity with the MTT assay. 8-OH-β-lapachones (14a, 14c, 14d) presented best results, showing low IC{sub 50} values and high selectivity for HCT-116 and HL-60 tumor cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Synthesis and anticancer effects of conjugates of doxorubicin and unsaturated fatty acids (LNA and DHA)

Doxorubicin (DOX) is a leading cytostatic drug with many adverse effects in use. We are still looking for methods that will allow us to preserve the therapeutic effect against the tumor cells and reduce the toxicity to the normal cells. In our work, we obtained amide derivatives of DOX by reaction of the amino group with α-linolenic (LNA) and docosahexaenoic (DHA) acids (2, 3), as well as double-substituted derivatives via amide and ester linkages (4, 5). The structures of the compounds were confirmed by Proton Nuclear Magnetic Resonance (1H NMR), Carbon-13 Nuclear Magnetic Resonance (13C NMR), and High Resolution Mass Spectrometry (HRMS) analyses. For all compounds 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxic effect on human cancer cell lines (SW480, SW620, and PC3) and Chinese hamster lung fibroblasts (V79) that were used as a control. The cytotoxic activity was established by calculation of the inhibitory concentration IC{sub 50}. In addition, a cytotoxic capacity against tumor cells for tested compounds was expressed as a selectivity factor (selectivity index, SI). Lactate dehydrogenase (LDH) assay was performed for all compounds to assess the level of cell damage. To explain the basic mechanism of cell death induction the Annexin V-FITC/IP flow cytometry analysis was investigated. We found that all studied conjugates exhibit lower cytotoxicity but higher selectivity than DOX. Among the all derivatives, the conjugates formed by the amide and ester linkages (4, 5) were found to be more promising compared with conjugates (2, 3) formed only by the amide linkage. They show high cytotoxicity toward the tumor cell lines and moderate cytotoxicity towards the normal cell line.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Synthesis of novel benzimidazole–oxadiazole derivatives as potent anticancer activity

DNA topoisomerase I regulates DNA topological structure in many cellular metabolic processes and is a validated target for the development of antitumor agents. In this work, a series of novel 2-[(5-(4-(5(6)-substituted-1H-benzimidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-substitutedphenyl)ethan-1-ones (4a–4s) derivatives have been synthesized and evaluated for DNA Topo I inhibition and cytotoxicity. The structures of the compounds (4a–4s) were confirmed by IR, {sup 1}H-NMR, {sup 13}C-NMR, 2D NMR, and mass spectroscopy. Anticancer activity of these compounds was assessed against two different human cancer cell lines A549 (human lung adenocarcinoma) and HepG2 (human liver cancer cell line), as well as normal mouse embryonic fibroblast cells (NIH3T3). IC{sub 50} values of compounds 4a, 4c, and 4f were highest than those exhibited for the reference drug cisplatin. Then, the inhibitory effect of 4a, 4c, and 4f compounds on topoisomerase I enzyme with the relaxation assay was investigated on supercoiled DNA using agarose gel electrophoresis. The Annexin V-FITC assay demonstrated that these compounds induce cell death by apoptosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Vegetable Oil Based Polyurethane Containing 1,2,3-Triazolium Functional Groups as Antimicrobial Wound Dressing

Preparation of antimicrobial polyurethane wound dressing membranes from a mixture of castor oil and a novel soybean oil-based polyol containing 1,2,3-triazolium rings (QTSBO) was described in this research. QTSBO was prepared through N-alkylation of 1,2,3-triazole functional soybean oil (TSBO) with methyl iodide, and TSBO was synthesized from an azidated soybean oil and propargyl alcohol through click reaction. The excellent tensile strength of these dressings under dry state and minimum deterioration of this property at fully hydrated state guaranteed the mechanical protection of wounds during the entire period of the healing process. The measured quantities of equilibrium water absorption and water vapor transmission rate for the optimized dressings confirmed the applicability of the selected formulations for the preservation of proper moist environment over low exuding wounds. The cyto-compatibility of dressings was verified by the excellent ability of the dressings to support the growth and proliferation of dermal fibroblasts. Due to the presence of 1,2,3-triazolium rings the dressing showed efficient antimicrobial activity against different bacterial and fungal stains. Therefore, these dressing could promote wound healing by preserving moist and hygienic environment over the wound bed.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Biocompatible Polyurethane Scaffolds Prepared from Glycerol Monostearate-Derived Polyester Polyol

Biodegradable polyester polyol was synthesized from oleochemical glycerol monostearate (GMS) and glutaric acid under a non-catalyzed and solvent-free polycondensation method. The chemical structure of GMS-derived polyester polyol (GPP) was elucidated by FTIR, {sup 1}H and {sup 13}C NMR, and molecular weight of GPP was characterized by GPC. The synthesized GPP with acid value of 3.03 mg KOH/g sample, hydroxyl value of 115.72 mg KOH/g sample and M{sub n} of 1345 g/mol was incorporated with polyethylene glycol (PEG) and polycaprolactone diol (PCL diol) to produce a water-blown porous polyurethane system via one-shot foaming method. The polyurethanes were optimized by evaluating glycerol as a crosslinker, silicone surfactant and water blowing agent on tensile properties of polyurethanes. All polyurethanes underwent structural change, and crystalline hard segments of polyurethanes were shifted to higher temperature suggested that hard segments undergone re-ordering process during enzymatic treatment. In terms of biocompatibility, polyurethane scaffold produced by reacting 100% w/w of GPP with isophorone diisocyanate and additives showed the highest cells viability of 3T3 mouse fibroblast (94%, day 1), and MG63 human osteosarcoma (107%, day 1) and better cell adhesion as compared to reference polyurethane produced by only PEG and PCL diol (3T3 cell viability: 8%; MG63 cell viability: 2%). The current work demonstrated GPP synthesized from renewable and environmental friendly resources produced polyurethanes that allows improvement in physico-chemical, mechanical and biocompatibility properties. By blending with increasing content of GPP, the water-blown porous polyurethane scaffold has shown great potential as biomaterial for soft and hard tissue engineering.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Physicochemical, Antimicrobial and Cytotoxic Characteristics of Corn Starch Film Containing Propolis for Wound Dressing

Modern dressings increase the rate of wound healing rather than just covering them. Dressing can protect the injured skin and keep it appropriately moist to speed up the healing process. In this study, the ethanolic extract of propolis loaded with corn starch was successfully prepared using solvent casting. Characterizations of the samples performed in respect to their mechanical properties were examined by scanning electron microscopy, contact angle, and attenuated total reflectance—fourier transform infrared spectroscopy, as well as antimicrobial capacities. The MTT assay using fibroblast cells showed the cell viability of corn starch in the ethanolic extract of propolis wound dressing. The results showed that by increasing the amount of ethanolic propolis extract from 0.25 to 1%, the tensile strength and the Young’s modulus of the samples were decreased, the elongation at the break increased about 15% as compared to the control films, and the contact angle properties were detected by a slightly hydrophobic character of the films in the antibacterial activity against Escherichia coli and Staphylococcus aureus even at low ethanolic extract of propolis concentrations (1%), mainly due to its phenolic compounds. Therefore, ethanolic extract of propolis loaded with corn starch film will be a potential candidate for wound dressing and skin tissue engineering.

36 MATERIALS SCIENCE↗
DOE OSTI2018

SPION@APTES@FA-PEG@Usnic Acid Bionanodrug for Cancer Therapy

In this work, we aimed to develop stable usnic acid (UA)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) as a potential drug carrier for in vitro analysis of MCF-7 (breast cancer cell line), HeLa (cervix cancer cell line), L929 (mouse fibroblast cell line), U87 (glioblastoma cell line, brain cancer), and A549 (human lung cancer cell line) cell lines. SPIONs were synthesized via the polyol method and functionalized with APTES using the Stöber method. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and carboxylated luteolin (CL) were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method, respectively. X-ray powder diffraction analysis confirmed the purity of the product with crystallite size of around 11 nm. Fourier-transformed infrared spectrophotometer (FT-IR) analyses explained the conjugation of all functional groups to the surface of SPIONs. The percentages of inorganic and organic content in the products were investigated via thermal gravimetric analyzer (TGA). For morphological analysis, a transmission electron microscope (TEM) was used. The superparamagnetic property of the product was also confirmed by vibrating sample magnetometer (VSM).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The Effect of Folic Acid- and Caffeic Acid-Functionalized SPION on Different Cancer Cell Lines

In this study, caffeic acid (CFA)- and folic acid (FA)-conjugated superparamagnetic iron oxide bio-nanocomposite (SPION@PEG-FA-@CFA) was prepared and its cytotoxic and apoptotic effects against murine fibroblast (L929), glioblastoma (U87), adenocarcinoma, human breast cancer (MCF-7), epithelioid cervix carcinoma (HeLa), and lung carcinoma (A549) have been determined. A real-time cell analyzer system (RTCA) for cytotoxicity, annexin assay and TUNEL, caspase 3/7 expression level, and caspase 3/7 activities for apoptosis were used. The RTCA showed that the cytotoxic effects of the bio-nanocomposite were higher in U87, MCF-7, and HeLa cells (which are folic acid-positive cells (FAR (+))). TUNEL, annexin, and caspase assay results indicated that the bio-nanocomposite caused apoptotic and necrotic impacts on cells. Necrotic and apoptotic cell ratios in FAR-positive cells (L929 and A549) were lesser than those in U87, MCF-7, and HeLa cells (FAR (+)). Therefore, the obtained results showed that the bio-nanocomposite can be used as a nano-medicine for biomedical application (cancer treatments). Moreover, this work can also be useful for designing other functionalized materials which could act as biomaterial. This study will be also informative for the researchers to design novel materials for biomedical applications.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Nanofibrous Scaffolds with Biomimetic Composition for Skin Regeneration

Treatments of skin injuries caused by trauma and diseases are among the most considerable medical problems. The use of scaffolds that can cover the wound area and support cellular ingrowth has shown great promise. However, mimicking the physicochemical properties of the native skin extracellular matrix (ECM) is essential for the successful integration of these scaffolds. Elastin has been known as the second main protein-based component of the native skin ECM. In this research, scaffolds containing gelatin, cellulose acetate, and elastin were fabricated using electrospinning. Subsequently, the effects of soluble elastin on the physical, mechanical, and biological properties of the prepared scaffolds were studied. The results confirmed that the presence of elastin in the composition changed the fiber morphology from straight to ribbon-like structure and decreased the swelling ratio and degradation rate of the scaffold. In vitro experiments showed that elastin-containing scaffolds supported the attachment and proliferation of fibroblast cells. Overall, the obtained results suggest the ternary blend of gelatin, cellulose acetate, and elastin as a good candidate for skin tissue engineering.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles

Triticum aestivum plant extracts are often used as a natural healer in traditional medicine but which particles mainly have role in these processes are not scientifically proven. In other words, no attempts have been made to investigate the effects of wheat exosomes in regenerative medicine applications or drug development up to now. The current study was first time performed to demonstrate the activity of wheat exosomes in wound healing process using in vitro approaches. Although its fundamental wound healing process remains a mystery, in the current study, the efficiency of wheat grass juice–derived exosomes on cell viability and migration was examined. Increasing concentrations up to 200 μg/mL of the wheat exosome have yielded astonishing proliferative and migratory effects on endothelial, epithelial, and dermal fibroblast cells. RT-PCR analysis also showed collagen type I; mRNA levels were approximately twofold higher in expression after treating with 200 μg/mL wheat exosome. Additionally, Annexin V staining of apoptotic cells accompanied with the cell cycle analysis resulted with the reduction of the apoptotic cell number with no dispersion to the cell cycle analysis while plant exosomes have also increased tube-like structure formation of the endothelial cells. All in all, this research suggests a brand-new opening for skin wound healing therapy strategy by using wheat-derived exosomes due to its proliferative and migratory characteristics. Plant exosomes require a further research both clinically and in in vivo for wound healing drug development. Moreover, plant exosome therapy strategies would be safer and economical alternative for clinical wound healing.

60 APPLIED LIFE SCIENCES↗
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

Establishment of CRISPR/Cas9-Mediated Knock-in System for Porcine Cells with High Efficiency

Since the birth of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, the new genome engineering technology has become a hot topic in the scientific community. However, for swine, the system of pig cells’ homology directed repair (HDR) is generally unstable and costly. Here, we aim to make knock-in of porcine cells more realizable. The Rosa26 locus was chosen for gene editing. Through the optimization of strategy, an efficient sgRNA was selected by TIDE analysis. Correspondingly, a vector system was constructed for gene insertion in pRosa26 locus by homologous recombination. A large percentage of cells whose gene is edited easily result in apoptosis. To improve the positive rate, culturing systems have been optimized. Sequence alignment and nuclear transfer confirmed that we got two knock-in cell lines and transgene primary porcine fetal fibroblasts (PFFs) successfully. Results showed that the gene editing platform we used can obtain genetically modified pig cells stably and efficiently. This system can contribute to pig gene research and production of transgenic pigs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Generation of mice deficient in RNA-binding motif protein 3 (RBM3) and characterization of its role in innate immune responses and cell growth

Highlights: {yields} We identified RNA-binding motif protein 3 (RBM3) as CpG-B DNA-binding protein. {yields} RBM3 translocates from the nucleus to the cytoplasm and co-localized with CpG-B DNA. {yields} We newly generated Rbm3-deficient (Rbm3{sup -/-}) mice. {yields} DNA-mediated cytokine gene induction was normally occured in Rbm3{sup -/-} cells. {yields}Rbm3{sup -/-} MEFs showed poorer proliferation rate and increased number of G2-phase cells. -- Abstract: The activation of innate immune responses is critical to host defense against microbial infections, wherein nucleic acid-sensing pattern recognition receptors recognize DNA or RNA from viruses or bacteria and activate downstream signaling pathways. In a search for new DNA-sensing molecules that regulate innate immune responses, we identified RNA-binding motif protein 3 (RBM3), whose role has been implicated in the regulation of cell growth. In this study, we generated Rbm3-deficient (Rbm3{sup -/-}) mice to study the role of RBM3 in immune responses and cell growth. Despite evidence for its interaction with immunogenic DNA in a cell, no overt phenotypic abnormalities were found in cells from Rbm3{sup -/-} mice for the DNA-mediated induction of cytokine genes. Interestingly, however, Rbm3{sup -/-} mouse embryonic fibroblasts (MEFs) showed poorer proliferation rates as compared to control MEFs. Further cell cycle analysis revealed that Rbm3{sup -/-} MEFs have markedly increased number of G2-phase cells, suggesting a hitherto unknown role of RBM3 in the G2-phase control. Thus, these mutant mice and cells may provide new tools with which to study the mechanisms underlying the regulation of cell cycle and oncogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Vitamin C enhances in vitro and in vivo development of porcine somatic cell nuclear transfer embryos

Highlights: {yields} Report for the first time that vitamin C has a beneficial effect on the development of porcine SCNT embryos. {yields} The level of acH4K5 and Oct4 expression at blastocyst-stage was up-regulated after treatment. {yields} A higher rate of gestation and increased number of piglets born were harvested in the treated group. -- Abstract: The reprogramming of differentiated cells into a totipotent embryonic state through somatic cell nuclear transfer (SCNT) is still an inefficient process. Previous studies revealed that the generation of induced pluripotent stem (iPS) cells from mouse and human fibroblasts could be significantly enhanced with vitamin C treatment. Here, we investigated the effects of vitamin C, to our knowledge for the first time, on the in vitro and in vivo development of porcine SCNT embryos. The rate of blastocyst development in SCNT embryos treated with 50 {mu}g/mL vitamin C 15 h after activation (36.0%) was significantly higher than that of untreated SCNT embryos (11.5%). The enhanced in vitro development rate of vitamin C-treated embryos was associated with an increased acetylation level of histone H4 lysine 5 and higher Oct4, Sox2 and Klf4 expression levels in blastocysts, as determined by real-time PCR. In addition, treatment with vitamin C resulted in an increased pregnancy rate in pigs. These findings suggest that treatment with vitamin C is beneficial for enhancement of the in vitro and in vivo development of porcine SCNT embryos.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Mxi1 regulates cell proliferation through insulin-like growth factor binding protein-3

Highlights: Black-Right-Pointing-Pointer Mxi1 regulates cell proliferation. Black-Right-Pointing-Pointer Expression of IGFBP-3 is regulated by Mxi1. Black-Right-Pointing-Pointer Inactivation of Mxi1 reduces IGFBP-3 expression in vitro and in vivo. -- Abstract: Mxi1, a member of the Myc-Max-Mad network, is an antagonist of the c-Myc oncogene and is associated with excessive cell proliferation. Abnormal cell proliferation and tumorigenesis are observed in organs of Mxi1-/- mice. However, the Mxi1-reltaed mechanism of proliferation is unclear. The present study utilized microarray analysis using Mxi1 mouse embryonic fibroblasts (MEFs) to identify genes associated with cell proliferation. Among these genes, insulin-like growth factor binding protein-3 (IGFBP-3) was selected as a candidate gene for real-time PCR to ascertain whether IGFBP-3 expression is regulated by Mxi1. Expression of IGFBP-3 was decreased in Mxi1-/- MEFs and Mxi1-/- mice, and the gene was regulated by Mxi1 in Mxi1 MEFs. Furthermore, proliferation pathways related to IGFBP-3 were regulated in Mxi1-/- mice compared to Mxi1+/+ mice. To determine the effect of Mxi1 inactivation on the induction of cell proliferation, a proliferation assay is performed in both Mxi1 MEFs and Mxi1 mice. Cell viability was regulated by Mxi1 in Mxi1 MEFs and number of PCNA-positive cells was increased in Mxi1-/- mice compared to Mxi1+/+ mice. Moreover, the IGFBP-3 level was decreased in proliferation defect regions in Mxi1-/- mice. The results support the suggestion that inactivation of Mxi1 has a positive effect on cell proliferation by down-regulating IGFBP-3.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Silencing p110{beta} prevents rapid depletion of nuclear pAkt

Highlights: Black-Right-Pointing-Pointer p110{beta} was essential for the statin- and ATP-induced depletion of nuclear pAkt and an associated inhibition of growth. Black-Right-Pointing-Pointer p110{beta} knock-out inhibited statin-induced changes in binding between FKBP51, pAkt and PTEN. Black-Right-Pointing-Pointer Data supports the hypothesis that nuclear pAkt is important for anti-cancer effects of statins. -- Abstract: The p110{beta} subunit in the class IA PI3K family may act as an oncogene and is critical for prostate tumor development in PTEN knockout mice. We tested the possible involvement of p110{beta} in a recently described rapid depletion of phosphorylated Akt (pAkt) in the nucleus. Previous work showed that this down-regulation is induced by extracellular ATP or by statins and is mediated by the purinergic receptor P2X7. Here, we used p110{beta} knock out mouse embryonic fibroblasts (MEFs) and siRNA-treated cancer cells. We found that p110{beta} is essential for ATP- or statin-induced nuclear pAkt depletion in MEFs and in several cancer cell lines including prostate cancer cells. ATP, statin or the selective P2X7 agonist BzATP also inhibited cell growth, and this inhibition was not seen in p110{beta} knock out cells. We also found that p110{beta} was necessary for statin-induced changes in binding between FKBP51, pAkt and PTEN. Our data show that p110{beta} is essential for the ATP- and statin-induced effects and support a role of nuclear pAkt in cancer development. They also provide support for a chemopreventive effect of statins mediated by depletion of nuclear pAkt.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

KLF10, transforming growth factor-{beta}-inducible early gene 1, acts as a tumor suppressor

Highlights: Black-Right-Pointing-Pointer KLF10{sup -/-} mice exhibited accelerated papilloma development after DMBA/TPA treatment. Black-Right-Pointing-Pointer KLF10{sup -/-} keratinocytes showed increased proliferation and apoptosis. Black-Right-Pointing-Pointer KLF10{sup -/-} MEFs yielded more colonies than wild-type one with H-Ras transfection. Black-Right-Pointing-Pointer KLF10 dose-dependently activated p21{sup WAF1/CIP1} transcription. Black-Right-Pointing-Pointer KLF10 is a tumor suppressor and that it targets p21{sup WAF1/CIP1} transcription. -- Abstract: Krueppel-like factor 10 (KLF10) has been suggested to be a putative tumor suppressor. In the present study, we generated KLF10 deficient mice to explore this hypothesis in vivo. KLF10 deficient mice exhibited increased predisposition to skin tumorigenesis and markedly accelerated papilloma development after DMBA/TPA treatment. On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis. In colony formation assays after oncogenic H-Ras transfection, KLF10 deficient mouse embryonic fibroblasts (MEFs) yielded more colonies than wild-type MEFs. Furthermore, KLF10 dose-dependently activated p21{sup WAF1/CIP1} transcription, which was independent of p53 and Sp1 binding sites in p21{sup WAF1/CIP1} promoter. This study demonstrates that KLF10 is a tumor suppressor and that it targets p21{sup WAF1/CIP1} transcription.

60 APPLIED LIFE SCIENCES↗