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Baicalein Inhibits MCF-7 Cell Proliferation In Vitro, Induces Radiosensitivity, and Inhibits Hypoxia Inducible Factor. 黄芩素体外抑制MCF-7细胞增殖、诱导辐射敏感性和抑制缺氧诱导因子
Shruti Gade, N. Gandhi
Hypoxia inducible factor (HIF) is a key transcription factor responsible for imparting adaptability to the cancer cells growing in tumors. HIF induces the modulation of glucose metabolism, angiogenesis, and prosurvival signaling. Therefore, HIF is one of the attractive targets to treat solid tumors. Results presented in this study indicate that Baicalein (BA) inhibits HIF stabilization and also reduces its transcription activity in MCF-7 cells in vitro. Furthermore, BA was found to have antiproliferative ability as determined by the MTT assay and clonogenic survival. BA also induces apoptosis in MCF-7 cells at the concentration of 50 µM. We also report the radiosensitization of MCF-7 cells when they are treated with BA, resulting in higher γ-radiation-induced DNA damage. BA is extensively used in Chinese medicine and is known to be nontoxic at pharmacological doses. Our studies indicate that BA is one of the attractive natural compounds suitable for further evaluation as an adjuvant therapy.
低氧诱导因子(Hypoxia inducible factor, HIF)是肿瘤中赋予癌细胞生长适应性的关键转录因子。HIF诱导糖代谢、血管生成和促生存信号的调节。因此,HIF是治疗实体瘤的有吸引力的靶点之一。本研究结果表明,黄芩苷(Baicalein, BA)在体外抑制MCF-7细胞中HIF的稳定,并降低其转录活性。此外,通过MTT试验和克隆生存测定,发现BA具有抗增殖能力。BA在50µM浓度下也能诱导MCF-7细胞凋亡。我们还报道了BA对MCF-7细胞的辐射致敏作用,导致更高的γ辐射诱导的DNA损伤。BA在中药中广泛使用,在药理学剂量下是无毒的。我们的研究表明,BA是一种有吸引力的天然化合物,适合作为辅助治疗的进一步评估。
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引用次数: 13
Iron and Iron-Related Proteins in Asbestosis. 石棉沉滞症中的铁和铁相关蛋白。
A. Ghio, E. Pavlisko, V. Roggli
We tested the postulate that iron homeostasis is altered among patients diagnosed to have asbestosis. Lung tissue from six individuals diagnosed to have had asbestosis at autopsy was stained for iron, ferritin, divalent metal transporter 1 (DMT1), and ferroportin 1 (FPN1). Slides from six individuals having pneumonectomy for lung cancer were employed as controls. Lung tissue from those patients with asbestosis demonstrated stainable iron, whereas control lung tissue did not. Staining for this metal was observed predominantly in airway and alveolar macrophages. Expression of the iron-related proteins ferritin, DMT1, and FPN1 was elevated in lung tissue from the six asbestosis patients relative to controls. This increased expression of iron-transport and iron-storage proteins was evident in both airway and alveolar epithelial cells. Asbestos bodies were abundant in lung tissue from patients diagnosed to have had asbestosis. While staining for iron, ferruginous bodies did not demonstrate uptake of antibodies for ferritin, DMT1, and FPN1. We conclude that iron homeostasis is altered in lung disease among those diagnosed to have asbestosis with an accumulation of the metal and a modified expression of iron-related proteins being evident.
我们测试了铁稳态在诊断为石棉沉滞的患者中发生改变的假设。对尸检时被诊断为石棉沉滞的6个人的肺组织进行了铁、铁蛋白、二价金属转运蛋白1 (DMT1)和铁转运蛋白1 (FPN1)的染色。6例肺癌全肺切除术患者的切片作为对照。来自石棉沉滞症患者的肺组织显示出可染铁,而对照肺组织则没有。这种金属的染色主要见于气道和肺泡巨噬细胞。与对照组相比,6例石棉肺患者肺组织中铁相关蛋白铁蛋白、DMT1和FPN1的表达升高。在气道和肺泡上皮细胞中,铁转运和铁储存蛋白的表达明显增加。石棉体在诊断为石棉沉滞症患者的肺组织中大量存在。在铁染色时,含铁小体未表现出铁蛋白、DMT1和FPN1抗体的摄取。我们的结论是,在诊断为石棉肺的患者中,肺部疾病中的铁稳态发生了改变,金属积累和铁相关蛋白的表达明显改变。
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引用次数: 9
Protective Role of Curcumin and Flunixin Against Acetic Acid-Induced Inflammatory Bowel Disease via Modulating Inflammatory Mediators and Cytokine Profile in Rats. 姜黄素和氟尼辛通过调节炎症介质和细胞因子谱对大鼠醋酸诱导的炎症性肠病的保护作用
B. Gopu, R. Dileep, Matukumalli Usha Rani, C.S.V. Satish Kumar, Matham Vijay Kumar, A. Gopala Reddy
Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study is to evaluate the effect of flunixin and curcumin in experimentally induced ulcerative colitis in rats. Animals were randomly divided into four groups, each consisting of 12 animals: normal control group, acetic acid group, curcumin-treated group, and flunixin-treated group. Induction of colitis by intracolonic administration of 4% acetic acid produced severe macroscopic inflammation in the colon, 14 days after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, edema, and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), colonic alkaline phosphatase (ALP), and myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxide formation and depleted reduced glutathione concentrations in colonic tissues. After induction of colitis, treatment with curcumin (50 mg/kg daily, p.o.) and flunixin (2.5 mg/kg daily, s.c.) decreased serum LDH, ALP, interleukin (IL)-1β, and tumor necrosis factor-α levels, as well as colonic MPO and lipid peroxide levels, whereas increased colonic prostaglandin E2 and IL-10 concentrations were observed. Moreover, effective doses of curcumin and flunixin were effective in restoring the histopathological changes induced by acetic acid administration. The findings of the present study provide evidence that flunixin may be beneficial in patients with inflammatory bowel disease.
溃疡性结肠炎是一种病因不明的慢性复发性炎症性肠病。探讨氟尼新和姜黄素对实验性溃疡性结肠炎大鼠的治疗作用。实验动物随机分为4组,每组12只:正常对照组、醋酸组、姜黄素处理组、氟尼新处理组。结肠内给予4%醋酸诱导结肠炎,在给予乙酸14天后,结肠损伤评分显示,在结肠内产生严重的宏观炎症。镜下结肠组织溃疡、水肿、炎性细胞浸润。生化研究显示血清乳酸脱氢酶(LDH)、结肠碱性磷酸酶(ALP)和髓过氧化物酶(MPO)水平升高。过氧化脂质形成升高和结肠组织中还原性谷胱甘肽浓度减少表明氧化应激。诱导结肠炎后,姜黄素(每天50 mg/kg, p.o)和氟尼辛(每天2.5 mg/kg, s.c)治疗可降低血清LDH、ALP、白细胞介素(IL)-1β和肿瘤坏死因子-α水平,以及结肠MPO和过脂质水平,同时观察到结肠前列腺素E2和IL-10浓度升高。有效剂量的姜黄素和氟尼辛对醋酸引起的组织病理改变有明显的恢复作用。本研究的结果提供了氟尼辛可能对炎症性肠病患者有益的证据。
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引用次数: 14
The first pilot study on characteristics and practice patterns of Kuwaiti breast cancer patients. 科威特乳腺癌患者的特点和实践模式的第一个试点研究。
F. Saleh, W. Reno, G. Ibrahim, A. Behbehani, H. Dashti, S. Asfar
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引用次数: 10
Lack of efficacy of the combination of pamidronate and vitamin D on regression of prostate cancer in the Dunning rat model. 帕米膦酸盐联合维生素D对Dunning模型大鼠前列腺癌消退缺乏疗效。
P. Herring, J. Ingels, L. Carbone, K. D. Barrow, D. Osborn, D. Dietzen, L. Pifer
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引用次数: 0
Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin. 姜黄素通过调节整合素受体、胶原酶活性以及Nm23和E-cadherin的表达来显示抗转移特性。
S. Ray, N. Chattopadhyay, A. Mitra, M. Siddiqi, A. Chatterjee
Curcumin (diferuloyl methane), the major pigment from the rhizome of Curcuma longa L., has been widely studied for its tumor-inhibiting properties. Recent studies indicate that curcumin can modify cell receptor binding, it also affects intracellular signalling reactions. Curcumin-treated B16F10 melanoma cells formed eight-fold fewer lung metastases in C57BL6 mice. In the cell adhesion assays, curcumin-treated cells showed a dose-dependent reduction in their binding to four extracellular matrix (ECM) proteins. The binding to fibronectin, vitronectin, and collagen IV decreased by over 50% in 24 hours, and by 100% after 48 hours of curcumin treatment, it persisted at this level even after 15 days of cultivating cells in curcumin-free medium. Curcumin-treated cells showed a marked reduction in the expression of alpha5beta1 and alpha(v)beta3 integrin receptors. In addition, curcumin treatment inhibited pp125 focal adhesion kinase (FAK), tyrosine phosphorylation of a 120 kD protein, and collagenase activity. Curcumin enhances the expression of antimetastatic proteins, tissue inhibitor metalloproteinase (TIMP)-2, nonmetastatic gene 23 (Nm23), and E-cadherin. In this article we report on the effect of curcumin on the expression of integrin, TIMP-2, Nm23, E-cadherin, adhesion, and metalloproteinase activity.
姜黄素是姜黄根茎中的主要色素,因其肿瘤抑制作用而被广泛研究。最近的研究表明,姜黄素可以改变细胞受体的结合,并影响细胞内的信号反应。姜黄素处理的B16F10黑色素瘤细胞在C57BL6小鼠中形成的肺转移减少了8倍。在细胞粘附试验中,姜黄素处理的细胞与四种细胞外基质(ECM)蛋白的结合呈剂量依赖性减少。与纤维连接蛋白、玻璃体连接蛋白和IV型胶原蛋白的结合在24小时内下降了50%以上,在姜黄素处理48小时后下降了100%,即使在无姜黄素的培养基中培养15天后也保持在这个水平。姜黄素处理的细胞显示alpha5beta1和α (v)beta3整合素受体的表达明显减少。此外,姜黄素处理抑制pp125黏附激酶(FAK)、酪氨酸磷酸化120 kD蛋白和胶原酶活性。姜黄素增强抗转移蛋白、组织抑制剂金属蛋白酶(TIMP)-2、非转移基因23 (Nm23)和E-cadherin的表达。在本文中,我们报道了姜黄素对整合素、TIMP-2、Nm23、E-cadherin、粘附和金属蛋白酶活性的影响。
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引用次数: 77
Bioassay-guided isolation of antimutagenic factors from fruits of Terminalia bellerica. 用生物测定法分离菝葜果实中抗诱变因子。
S. Kaur, Saroj Arora, S. Kaur, Subodh Kumar
In the course of our search for novel polyphenolic antimutagenic agents from medicinal plants, we examined water, acetone, and chloroform extracts of Terminalia bellerica for their antimutagenic potency using the Ames Salmonella/microsome assay. Acetone extract exhibited variable inhibitory activity of 65.6%, and 69.7% with 4-O-nitrophenylenediamine (NPD) and sodium azide, respectively (as direct-acting mutagens), and 81.4% with 2-aminofluorene (2AF) (an S9-dependent mutagen), in the preincubation mode of experimentation. Inhibition with chloroform and water extracts was rather insignificant. Studies are well underway to isolate and identify the active polyphenolic compounds from acetone extract, which could be used as effective chemopreventive agents in the future.
在我们从药用植物中寻找新的多酚类抗诱变剂的过程中,我们使用Ames沙门氏菌/微粒体试验检测了Terminalia bellerica的水、丙酮和氯仿提取物的抗诱变效力。在实验的预孵育模式下,丙酮提取物对4- o -硝基苯二胺(NPD)和叠氮化钠的抑制活性分别为65.6%和69.7%,对2-氨基芴(2AF) (s9依赖性诱变剂)的抑制活性为81.4%。氯仿和水提取物的抑制作用不明显。从丙酮提取物中分离和鉴定活性多酚类化合物的研究正在进行中,这些活性多酚类化合物有望在未来成为有效的化学预防剂。
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引用次数: 18
Studies on correlation of antimutagenic and antiproliferative activities of Juglans regia L. 核桃抗诱变与抗增殖活性的相关性研究。
K. Kaur, Husheem Michael, Saroj Arora, P. Härkönen, Subodh Kumar
We investigated the effect of water and acetone extract of Juglans regia L. to evaluate its antimutagenic and antiproliferative activities. The antimutagenic study using TA98 and TA100 tester strains of Salmonella revealed the water and acetone extracts to be more effective than the benzene and chloroform extracts in inhibiting the revertants induced by 2-aminoflourene (2AF) in TA100 tester strains. The most effective extracts in the Ames assay were further evaluated using the Lucifer luciferase assay and in time course studies for antiproliferative activities using the Hoechst staining to observe apoptotic cell deaths. The acetone extract showed a correlation of antimutagenic activities in the Ames assay with its antiproliferative effect in different cell lines, while the water extract exerted its effect distinctly in each cell line. Further studies are still needed to evaluate the cytotoxicity in experiments carried out in vivo.
研究核桃水提取物和丙酮提取物的抗诱变和抗增殖活性。对沙门氏菌TA98和TA100试验菌株的抗诱变研究表明,水和丙酮提取物比苯和氯仿提取物更能抑制2-氨基芴(2AF)对TA100试验菌株的诱变作用。Ames实验中最有效的提取物使用Lucifer荧光素酶实验进一步评估,并使用Hoechst染色观察凋亡细胞死亡的抗增殖活性。在Ames实验中,丙酮提取物的抗诱变活性与其对不同细胞系的抗增殖作用呈相关性,而水提取物对不同细胞系的抗诱变作用均明显。还需要进一步的研究来评估在体内进行的细胞毒性实验。
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引用次数: 32
Fluorescence in situ hybridization (FISH) in genetic toxicology. 荧光原位杂交(FISH)在遗传毒理学中的应用。
A. Natarajan
Structural and numerical chromosomal aberrations have been considered important biological end points in genotoxic studies. Conventional solid staining (such as Giemsa) has been employed to evaluate the frequencies ofinduced chromosomal aberrations following exposure to chemical or physical agents. Recently, molecular cytogenetic techniques that have become available, such as fluorescence in situ hybridization (FISH) using chromosome-specific or chromosomal regions-specific DNA libraries, have increased the resolution of detection of aberrations. The present paper reviews briefly the results obtained from basic and applied studies using the FISH technique.
在遗传毒性研究中,染色体结构和数值畸变被认为是重要的生物学终点。传统的实体染色(如吉姆萨染色)已被用于评估暴露于化学或物理试剂后诱导染色体畸变的频率。最近,可用的分子细胞遗传学技术,如利用染色体特异性或染色体区域特异性DNA文库的荧光原位杂交(FISH),提高了检测畸变的分辨率。本文简要介绍了FISH技术的基础研究和应用研究的结果。
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引用次数: 15
Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors. 环氧化酶-2抑制剂预防结肠癌的新途径
Bandaru S. Reddy, C. Rao
During recent years, multidisciplinary studies in epidemiology and molecular biology, as well as preclinical studies, have contributed much to our understanding of the etiology of colorectal cancer; more importantly they have enabled us to approach its prevention. An impressive body of epidemiological data suggests an inverse relationship between colorectal cancer risk and regular use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. Clinical trials with NSAIDs have demonstrated that NSAID treatment caused regression of preexisting colon adenomas in patients with familial adenomatous polyposis. Preclinical efficacy studies have provided compelling evidence that several phytochemicals with antiinflammatory properties and NSAIDs act to retard, block, or reverse colon carcinogenesis. Equally exciting are opportunities for effective chemoprevention with selective cyclooxygenase-2 (COX-2) inhibitors including celecoxib and rofecoxib in a variety of preclinical models of colon cancer. Naturally occurring COX-2 inhibitors such as curcumin and certain phytosterols have been proven to be effective as chemopreventive agents against colon carcinogenesis with minimal gastrointestinal toxicity. Multistep process of carcinogenesis has provided substantial insights into the mechanisms by which naturally occurring and synthetic antiinflammatory agents modulate these events leading to suppression of tumorigenesis. Growing knowledge in this area has brought about innovative approaches using a combination of agents with different modes of action as a means of increasing efficacy and minimizing toxicity. The natural history of colorectal cancer, from dysplastic aberrant crypts to adenomas and adenocarcinomas, offers multiple opportunities for assessment and intervention. Of further importance would be to identify molecular targets that are critical in the growth and survival of the malignant colorectal cell and are modulated by NSAIDs and COX-2 inhibitors.
近年来,流行病学和分子生物学的多学科研究以及临床前研究为我们了解结直肠癌的病因做出了很大贡献;更重要的是,它们使我们能够采取预防措施。令人印象深刻的流行病学数据表明,结直肠癌风险与定期使用非甾体类抗炎药(NSAIDs)(包括阿司匹林)之间呈反比关系。非甾体抗炎药的临床试验表明,非甾体抗炎药治疗可使家族性腺瘤性息肉病患者原有的结肠腺瘤消退。临床前疗效研究提供了令人信服的证据,证明几种具有抗炎特性的植物化学物质和非甾体抗炎药可以延缓、阻断或逆转结肠癌的发生。同样令人兴奋的是,选择性环氧化酶-2 (COX-2)抑制剂(包括塞来昔布和罗非昔布)在多种结肠癌临床前模型中的有效化学预防机会。天然存在的COX-2抑制剂,如姜黄素和某些植物甾醇,已被证明是有效的化学预防剂,对结肠癌的发生具有最小的胃肠道毒性。多步骤的癌变过程为自然发生和合成抗炎剂调节这些事件从而抑制肿瘤发生的机制提供了实质性的见解。这一领域知识的增长带来了创新的方法,使用具有不同作用方式的药物组合作为提高疗效和减少毒性的手段。结直肠癌的自然历史,从发育异常的隐窝到腺瘤和腺癌,为评估和干预提供了多种机会。进一步重要的是确定对恶性结直肠癌细胞生长和存活至关重要的分子靶点,并由非甾体抗炎药和COX-2抑制剂调节。
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引用次数: 90
期刊
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
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