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141.
BPD-MA光动力作用对膀胱癌细胞凋亡及bcl-2蛋白表达的影响 总被引:3,自引:0,他引:3
目的:研究激光活化BPD-MA光动力诱导肿瘤细胞凋亡及其可能机制。方法:应用流式细胞仪分析BPD-MA光动力作用后细胞凋亡及免疫组化染色检测凋亡相关蛋白bcl-2蛋白表达水平。结果:激光活化BPD-MA光动力实验组人膀胱癌细胞株BIU-87凋亡发生率达26.11±2.59%,与对照组相比,差异非常显著性(P<0.01);光动力作用后膀胱癌细胞线粒体相关调控蛋白bcl-2表达显著低于对照组(P<0.05)。结论:激光活化BPD-MA光动力作用具有诱导人膀胱癌细胞株BIU-87凋亡的生物效应,而线粒体相关调控蛋白bcl-2表达水平的降低可能是激光活化BPD-MA光动力诱导人膀胱癌细胞株BIU-87凋亡的重要机制之一。 相似文献
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143.
Wen-Hsiung Chan 《International journal of molecular sciences》2014,15(6):10751-10765
We examined the cytotoxic effects of dillapiole, a phenylpropanoid with antileishmanial, anti-inflammatory, antifungal, and acaricidal activities, on the blastocyst stage of mouse embryos, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation via embryo transfer. Blastocysts treated with 2.5–10 μM dillapiole exhibited a significant increase in apoptosis and corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with dillapiole were lower than those of their control counterparts. Moreover, in vitro treatment with 2.5–10 μM dillapiole was associated with increased resorption of post-implantation embryos and decreased fetal weight. Our results collectively indicate that dillapiole induces apoptosis and retards early post-implantation development, both in vitro and in vivo. However, the extent to which this organic compound exerts teratogenic effects on early human development is not known at present. Further studies are required to establish effective protection strategies against the cytotoxic effects of dillapiole. 相似文献
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Niels A. J. Cremers Ditte M. S. Lundvig Stephanie C. M. van Dalen Rik F. Schelbergen Peter L. E. M. van Lent Walter A. Szarek Raymond F. Regan Carine E. Carels Frank A. D. T. G. Wagener 《International journal of molecular sciences》2014,15(10):17974-17999
Mesenchymal stem cell (MSC) administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO) generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO) and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs) from wild type (WT) and HO-2 knockout (KO) mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC survival, WT and HO-2 KO ASCs were pre-treated with HO-activity modulators, or downstream effector molecules biliverdin, bilirubin, and CO before co-exposure of ASCs to a toxic dose of H2O2. Surprisingly, sensitivity to H2O2-mediated cell death was similar in WT and HO-2 KO ASCs. However, pre-induction of HO-1 expression using curcumin increased ASC survival after H2O2 exposure in both WT and HO-2 KO ASCs. Simultaneous inhibition of HO-activity resulted in loss of curcumin-mediated protection. Co-treatment with glutathione precursor N-Acetylcysteine promoted ASC survival. However, co-incubation with HO-effector molecules bilirubin and biliverdin did not rescue from H2O2-mediated cell death, whereas co-exposure to CO-releasing molecules-2 (CORM-2) significantly increased cell survival, independently from HO-2 expression. Summarizing, our results show that curcumin protects via an HO-1 dependent mechanism against H2O2-mediated apoptosis, and likely through the generation of CO. HO-1 pre-induction or administration of CORMs may thus form an attractive strategy to improve MSC therapy. 相似文献
146.
Synthesis and Biological Evaluation of Benzo[b]furans as Inhibitors of Tubulin Polymerization and Inducers of Apoptosis
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Dr. Ahmed Kamal N. V. Subba Reddy V. Lakshma Nayak V. Saidi Reddy B. Prasad Vijaykumar D. Nimbarte Vunnam Srinivasulu M. V. P. S. Vishnuvardhan Prof. C. Suresh Reddy 《ChemMedChem》2014,9(1):117-128
A series of benzo[b]furans was synthesized with modification at the 5‐position of the benzene ring by introducing C‐linked substituents (aryl, alkenyl, alkynyl, etc.). These compounds were evaluated for their antiproliferative activities, inhibition of tubulin polymerization, and cell‐cycle effects. Some compounds in this series displayed excellent activity in the nanomolar range against lung cancer (A549) and renal cell carcinoma (ACHN) cancer cell lines. (6‐Methoxy‐5‐((4‐methoxyphenyl)ethynyl)‐3‐methylbenzofuran‐2‐yl)(3,4,5‐trimethoxyphenyl)methanone ( 26 ) and (E)‐3‐(6‐methoxy‐3‐methyl‐2‐(1‐(3,4,5‐trimethoxyphenyl)vinyl)benzofuran‐5‐yl)prop‐2‐en‐1‐ol ( 36 ) showed significant activity in the A549 cell line, with IC50 values of 0.08 and 0.06 μM , respectively. G2/M cell‐cycle arrest and subsequent apoptosis was observed in the A549 cell line after treatment with these compounds. The most active compound in this series, 36 , also inhibited tubulin polymerization with a value similar to that of combretastatin A‐4 (1.95 and 1.86 μM , respectively). Furthermore, detailed biological studies such as Hoechst 33258 staining, DNA fragmentation and caspase‐3 assays, and western blot analyses with the pro‐apoptotic protein Bax and the anti‐apoptotic protein Bcl‐2 also suggested that these compounds induce cell death by apoptosis. Molecular docking studies indicated that compound 36 interacts and binds efficiently with the tubulin protein. 相似文献
147.
Stereoselective Reduction of 1‐O‐Isopropyloxygenipin Enhances Its Neuroprotective Activity in Neuronal Cells from Apoptosis Induced by Sodium Nitroprusside
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Rikang Wang Jian Yang Sufen Liao Gaokeng Xiao Jun Luo Lang Zhang Peter J. Little Prof. Heru Chen Prof. Wenhua Zheng 《ChemMedChem》2014,9(7):1397-1401
Genipin is a Chinese herbal medicine with both neuroprotective and neuritogenic activity. Because of its unstable nature, efforts have been to develop more stable genipin derivatives with improved biological activities. Among the new compounds reported in the literature, (1R)‐isopropyloxygenipin (IPRG001) is a more stable but less active compound compared with the parent, genipin. Here, two new IPRG001 derivatives generated by stereoselective reduction of the C6=C7 double bond were synthesized. The 1R and 1S isomers of (4aS,7S,7aS)‐methyl‐7‐(hydroxymethyl)‐1‐isopropoxy‐1,4a,5,6,7,7a‐hexahydrocyclopenta[c]pyran‐4‐carboxylate ( CHR20 and CHR21 ) were shown to be very stable both in high‐glucose cell culture medium and in mice serum at 37 °C. Evaluation using an MTT assay and Hoechst staining showed that CHR20 and CHR21 promote the survival of rat adrenal pheochromocytoma (PC12) and retinal neuronal (RGC‐5) cells from injury induced by sodium nitroprusside (SNP). The neuroprotective effects of CHR20 and CHR21 were greater than both isomers of IPRG001, the parent compounds. These results indicate that reduction of 1‐O‐isopropyloxygenipin enhances its neuroprotective activity without affecting its stability. 相似文献
148.
Dr. Xiu‐Ying Qin Dr. Ya‐Nan Liu Dr. Qian‐Qian Yu Dr. Li‐Cong Yang Ying Liu Dr. Yan‐Hui Zhou Prof. Dr. Jie Liu 《ChemMedChem》2014,9(8):1665-1671
A novel copper(II) complex with mixed ligands including β‐[(3‐formyl‐5‐methyl‐2‐hydroxy‐benzylidene)amino]propionic acid anion and 1,10′‐phenanthroline was synthesized, and its crystal structure was thoroughly characterized. It exerted excellent inducing apoptosis, anti‐angiogenesis and antiproliferative properties in vitro. The complex can bind human serum albumin (HSA) at physiological pH conditions. Remarkably, it can induce formation of the mixed parallel/antiparallel G‐quadruplex structures in the G‐rich sequence of the proximal vascular endothelial growth factor (VEGF) promoter, and stabilize these G‐quadruplex structures, which provide an opportunity for anti‐angiogenesis chemotherapeutics. Furthermore, the complex showed a strong uptake, and exhibited multiple anticancer functions by inhibiting the expression of p‐Akt and p‐Erk1/2 proteins and by upregulating the levels of reactive oxygen species (ROS). Because of the reported results, this new copper(II) complex qualifies itself as a potential anticancer drug candidate. 相似文献
149.
Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κP,κS‐Coordinated Ph2PCH2CH2CH2S(O)xPh (x=0–2) Ligands
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Gerd Ludwig Ivan Ranđelović Dr. Danijela Maksimović‐Ivanić Dr. Sanja Mijatović Mirna Z. Bulatović Dr. Djordje Miljković Prof. Marcus Korb Prof. Dr. Heinrich Lang Prof. Dr. Dirk Steinborn Prof. Dr. Goran N. Kaluđerović 《ChemMedChem》2014,9(7):1586-1593
Iridium(III) complexes of the type [Ir(η5‐C5Me5)Cl2{Ph2PCH2CH2CH2S(O)xPh‐κP}] (x=0–2; 1 – 3 ) and [Ir(η5‐C5Me5)Cl{Ph2PCH2CH2CH2S(O)xPh‐κP,κS}][PF6] (x=0–1; 4 and 5 ) with 3‐(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2PCH2CH2CH2S(O)xPh were designed, synthesized, and characterized fully, including X‐ray diffraction analyses for complexes 3 and 4 . In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF‐7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC50 values up to about 0.1 μM , representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal‐based anticancer agents. 相似文献
150.
Zhong-Tao Liu Li Xiong Zhi-Peng Liu Xiong-Ying Miao Liang-Wu Lin Yu Wen 《Nanoscale research letters》2014,9(1):319
This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers'' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II (p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro. 相似文献