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991.
《Free radical research》2013,47(6):707-716
AbstractBleomycin (BLM) is an anti-cancer drug that can induce formation of reactive oxygen species (ROS). To investigate the association between up-regulation of antioxidant enzymes and coenzyme Q10 (CoQ10) in acquired BLM resistance, one BLM-resistant clone, SBLM24 clone, was selected from a human oral cancer cell line, SCC61 clone. The BLM resistance of SBLM24 clone relative to a sub-clone of SCC61b cells was confirmed by analysis of clonogenic ability and cell cycle arrest. CoQ10 levels and levels of Mn superoxide dismutase, glutathione peroxidase 1, catalase and thioredoxin reductase 1 were augmented in SBLM24 clone although there was also a mild increase in the expression of BLM hydrolase. Suppression of CoQ10 levels by 4-aminobenzoate sensitized BLM-induced cytotoxicity. The results of suppression on enhanced ROS production by BLM and the cross-resistance to hydrogen peroxide in SBLM24 clone further demonstrated the development of adaptation to oxidative stress during the formation of acquired BLM resistance. 相似文献
992.
Chuying Ma Guangfu Yin Danhong Yan Xueling He Li Zhang Yan Wei Zhongbing Huang 《Journal of peptide science》2013,19(12):730-736
Discovery of peptide ligands that can target human ovarian cancer and deliver chemotherapeutics offers new opportunity for cancer therapy. The advent of phage‐displayed peptide library facilitated the screening of such peptides. In vivo screening that set in a microanatomic and functional context was applied in our study, and a novel peptide WSGPGVWGASVK targeting ovarian cancer was isolated. The phage clone PC3‐1 displaying peptide WSGPGVWGASVK can gain effective access to accumulate in the tumor sites after intravenous injection while reducing its accumulation in normal organs. Positive immunostaining of PC3‐1 was located in both sites of tumor cells and tumor blood vessels, which resulted in a diffuse binding pattern through the tumor. In vitro study results confirmed the capability of peptide WSGPGVWGASVK binding to and being internalized by both tumor cells and angiogenic endothelial cells. Flow cytometry analysis revealed that the peptide bound to SKOV3 cells with Kd value of 5.43 ± 0.4 μM. Taken together, it suggested that peptide WSGPGVWGASVK is a lead candidate for delivering therapeutics to penetrate into tumors. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
993.
《Free radical research》2013,47(4):466-477
AbstractIn this study, we studied the mechanism of the cytotoxicity of malabaricone C (mal C) against human breast cancer MCF-7 cell line. Mal C dose-dependently increased the sub G1 cell population, associated with cytoplasmic oligonucleosome formation and chromatin condensation. The mal C-induced apoptosis led to mitochondrial damage as revealed by fluorescence microscopy and flow cytometry of the JC-1-stained cells as well as from the release of mitochondrion-specific nuclease proteins AIF and endo G. Mal C also released intracellular Ca2+ from the MCF-7 cells, but the Ca2+-modulators BAPTA-AM and Ru360 only partially abrogated the apoptosis. The calpain activation by mal C did not have any effect on its cytotoxicity. On the other hand, after mal C treatment significant lysosomal membrane permeabilization (LMP), along with release of cathepsin B, as well as Bid-cleavage and its translocation to mitochondria were observed much earlier than the mitochondrial damage. This suggested that cytotoxicity of mal C against human MCF-7 human breast cancer cell line may proceed through LMP as the initial event that triggered a caspase-independent, but cathepsin B and t-Bid-dependent intrinsic mitochondrial apoptotic pathway. A significant accumulation of cells in the S or G2-M phases along with upregulation of the cyclins E and A due to mal C exposure promises it to be a potential anti-cancer agent. 相似文献
994.
《Journal of receptor and signal transduction research》2013,33(3):220-228
The effect of carvedilol on cytosolic free Ca2+ concentrations ([Ca2+]i) in OC2 human oral cancer cells is unknown. This study examined if carvedilol altered basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent probe. Carvedilol at concentrations between 10 and 40 µM increased [Ca2+]i in a concentration-dependent fashion. The Ca2+ signal was decreased by 50% by removing extracellular Ca2+. Carvedilol-induced Ca2+ entry was not affected by the store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, but was enhanced by activation or inhibition of protein kinase C. In Ca2+-free medium, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin did not change carvedilol-induced [Ca2+]i rise; conversely, incubation with carvedilol did not reduce thapsigargin-induced Ca2+ release. Pretreatment with the mitochondrial uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) inhibited carvedilol-induced [Ca2+]i release. Inhibition of phospholipase C with U73122 did not alter carvedilol-induced [Ca2+]i rise. Carvedilol at 5–50 µM induced cell death in a concentration-dependent manner. The death was not reversed when cytosolic Ca2+ was chelated with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA/AM). Annexin V/propidium iodide staining assay suggests that apoptosis played a role in the death. Collectively, in OC2 cells, carvedilol induced [Ca2+]i rise by causing phospholipase C-independent Ca2+ release from mitochondria and non-endoplasmic reticulum stores, and Ca2+ influx via protein kinase C-regulated channels. Carvedilol (up to 50 μM) induced cell death in a Ca2+-independent manner that involved apoptosis. 相似文献
995.
996.
997.
Kaori Fukushima Kaede Takahashi Mirai Kusaka Kaichi Ishimoto Kanako Minami Shiho Otagaki 《Journal of receptor and signal transduction research》2013,33(4):311-315
AbstractFree fatty acid (FFA) receptors belong to a member of G-protein-coupled receptors. GPCR 120 (GPR120) and GPR40 are identified as FFA receptors and activated via the binding of long- and medium-chain FFAs. The aim of this study was to assess the effects of GPR120 and GPR40 on cell motility and growth in breast cancer cells treated with tamoxifen (TAM). MCF-7 cells were continuously treated with TAM for approximately 6?months. The expression level of GPR40 gene was markedly higher in the long-term TAM treated (MCF-TAM) cells than in MCF-7 cells. In cell motility assay, MCF-TAM cells indicated the high cell motile activity, compared with MCF-7 cells. The cell motile activity of MCF-TAM cells was suppressed by a selective GPR40 antagonist, GW1100. To evaluate the effects of GPR40 on cell growth activity under estrogen-free conditions, cells were maintained in serum-free DMEM without phenol red for 2?days. In estrogen-free conditioned medium, the cell growth rate of MCF-TAM cells was significantly higher than that of MCF-7 cells. In addition, treatment of GW1100 reduced the cell growth rate of MCF-TAM cells. These results suggest that the cell motile and growth activities may be positively regulated through the induction of GPR40 by the long-term TAM treatment in MCF-7 cells. 相似文献
998.
《Journal of receptor and signal transduction research》2013,33(6):578-584
AbstractLysophosphatidic acid (LPA) is a bioactive phospholipid that is involved in signal transduction between cells. Plasma and ascites levels of LPA are increased in ovarian cancer patients even in the early stages and thus LPA is considered as a potential diagnostic marker for this disease. This review presents the current knowledge regarding LPA signaling in epithelial ovarian cancer. LPA stimulates proliferation, migration and invasion of ovarian cancer cells through regulation of vascular endothelial growth factor, matrix metalloproteinases, urokinase plasminogen activator, interleukin-6, interleukin-8, CXC motif chemokine ligand 12/CXC receptor 4, COX2, cyclin D1, Hippo-Yap and growth-regulated oncogene α concentrations. In this article, all of these targets and signal pathways involved in LPA influence are described. 相似文献
999.
《Journal of receptor and signal transduction research》2013,33(5):462-467
AbstractDuffy antigen receptor for chemokines (DARC) is a silent chemokine receptor which selectively binds angiogenic chemokines without inducing conventional signaling responses. DARC has been reported to inhibit the development of multiple cancers through clearance of angiogenic chemokines. However, its role in colorectal cancer (CRC) remains unclear. We investigated the expression of DARC in CRC and explored correlation of DARC expression with clinical pathological features and microvessel density (MVD). The protein expression levels of DARC were detected by immunohistochemistry in 90 CRC and 64 paired unaffected tissues. The mRNA levels of DARC were detected by quantitative real-time PCR in 15 CRC and paired unaffected tissues. MVD in CRC was also assessed by immunohistochemistry of CD34. We found that the mRNA and protein expression levels of DARC were significantly lower in CRC than in the unaffected tissues (p?<?0.05). The DARC protein expression levels were positively correlated with DARC mRNA expression levels in both CRC (p?<?0.001) and unaffected tissues (p?<?0.001). We also found that DARC expression was significantly correlated with tumor differentiation (p?<?0.001), lymph node metastasis (p?<?0.01) and TNM stage (p?<?0.05). Moreover, we observed a strong negative relationship between DARC expression and MVD in CRC (p?<?0.001). We showed that DARC expression is down-regulated in CRC and associated with clinical pathological features and MVD of CRC. DARC might be involved in tumorigenesis, progression, angiogenesis, and metastasis of CRC. 相似文献
1000.
《Journal of receptor and signal transduction research》2013,33(6):353-358