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https://www.readbyqxmd.com/read/28099142/the-pentapeptide-gly-thr-gly-lys-thr-confers-sensitivity-to-anti-cancer-drugs-by-inhibition-of-cage-binding-to-gsk3%C3%AE-and-decreasing-the-expression-of-cyclind1
#1
Youngmi Kim, Hyuna Kim, Deokbum Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Doyong Jeon, Dooil Jeoung
We previously reported the role of cancer/testis antigen CAGE in the response to anti-cancer drugs. CAGE increased the expression of cyclinD1, and pGSK3βSer9, an inactive GSK3β, while decreasing the expression of phospho-cyclinD1Thr286. CAGE showed binding to GSK3β and the domain of CAGE (amino acids 231-300) necessary for binding to GSK3β and for the expression regulation of cyclinD1 was determined. 269GTGKT273 peptide, corresponding to the DEAD box helicase domain of CAGE, decreased the expression of cyclinD1 and pGSK3βSer9 while increasing the expression of phospho-cyclinD1Thr286...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#2
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28074910/myosin-phosphatase-and-rhoa-activated-kinase-modulate-arginine-methylation-by-the-regulation-of-protein-arginine-methyltransferase-5-in-hepatocellular-carcinoma-cells
#3
Adrienn Sipos, Judit Iván, Bálint Bécsi, Zsuzsanna Darula, István Tamás, Dániel Horváth, Katalin F Medzihradszky, Ferenc Erdődi, Beáta Lontay
Myosin phosphatase (MP) holoenzyme is a protein phosphatase-1 (PP1) type Ser/Thr specific enzyme that consists of a PP1 catalytic (PP1c) and a myosin phosphatase target subunit-1 (MYPT1). MYPT1 is an ubiquitously expressed isoform and it targets PP1c to its substrates. We identified the protein arginine methyltransferase 5 (PRMT5) enzyme of the methylosome complex as a MYPT1-binding protein uncovering the nuclear MYPT1-interactome of hepatocellular carcinoma cells. It is shown that PRMT5 is regulated by phosphorylation at Thr80 by RhoA-associated protein kinase and MP...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063352/a-tumor-targeted-activatable-phthalocyanine-tetrapeptide-doxorubicin-conjugate-for-synergistic-chemo-photodynamic-therapy
#4
Mei-Rong Ke, Shao-Fang Chen, Xiao-Hui Peng, Qiao-Feng Zheng, Bi-Yuan Zheng, Chih-Kuang Yeh, Jian-Dong Huang
Chemo-photodynamic therapy is a promising strategy for cancer treatments. However, it remains a challenge to develop a chemo-photodynamic therapeutic agent with little side effect, high tumor-targeting, and efficient synergistic effect simultaneously. Herein, we report a zinc(II) phthalocyanine (ZnPc)-doxorubicin (DOX) prodrug linked with a fibroblast activation protein (FAP)-responsive short peptide with the sequence of Thr-Ser-Gly-Pro for chemo-photodynamic therapy. In the conjugate, both photosensitizing activity of ZnPc and cytotoxicity of DOX are inhibited obviously...
December 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28035373/cancer-associated-peritoneal-mesothelial-cells-lead-the-formation-of-pancreatic-cancer-peritoneal-dissemination
#5
Toshiya Abe, Kenoki Ohuchida, Kazuhiro Koikawa, Sho Endo, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura
The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between the pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28034642/insights-into-the-mechanism-of-apoptin-s-exquisitely-selective-anti-tumor-action-from-atomic-level-characterization-of-its-conformation-and-dynamics
#6
Santiago Ruiz-Martínez, David Pantoja-Uceda, Jessica Castro, Maria Vilanova, Marc Ribó, Marta Bruix, Antoni Benito, Douglas V Laurents
Apoptin is a 121 residue protein which forms large, soluble aggregates and possesses an exceptionally selectively cytotoxic action on cancer cells. In the accompanying paper, we described the design, production and initial characterization of an Apoptin truncated variant called H6-ApopΔProΔLeu. Whereas both the variant and wild type protein possess similar selective cytotoxicity against cancer cells following transfection, only the variant is cytotoxic when added externally. Remarkably, as observed by gel filtration chromatography and dynamic light scattering, H6-ApopΔProΔLeu lacks the tendency of wild type Apoptin to form large aggregates, which greatly facilitated the study of its biological properties...
January 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28018099/understanding-the-role-of-pin1-in-hepatocellular-carcinoma
#7
REVIEW
Chi-Wai Cheng, Ka-Wai Leong, Eric Tse
PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27982018/sio2-antisense-molecules-covered-by-nepetalactone-extracted-from-nepeta-gloeocephala-inhibits-ilk-phosphorylation-and-downstream-pkb-akt-signaling-in-hela-cells
#8
M Dehghany Ashkezary, F Aboee-Mehrizi, P Moradi
In this study, the anticancer property of SiO2@antisense molecules (SiO2@AMs) and SiO2@AM covered by nepetalactone (SiO2@AM/CN), extracted from Nepeta gloeocephala, was investigated. Here integrin-linked kinase (ILK) phosphorylation and protein kinase B/AKT (PKB/AKT) signaling was studied when HeLa cells were exposed to SiO2@AM and SiO2@AM/CN. First, N. gloeocephala was identified at the Iranian National Herbarium. Then, its essential oil (EO) was obtained by the hydrodistillation method. In the next step, 4aα,7α,7aα-nepetalactone was extracted from the EO, based on the spectroscopic data...
December 16, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27956712/induction-of-integrin-signaling-by-steroid-sulfatase-in-human-cervical-cancer-cells
#9
Dong-Jin Ye, Yeo-Jung Kwon, Sangyun Shin, Hyoung-Seok Baek, Dong-Won Shin, Young-Jin Chun
Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin β1 and fibronectin, a ligand of integrin α5β1...
December 13, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27956097/binding-studies-and-biological-evaluation-of-%C3%AE-carotene-as-a-potential-inhibitor-of-human-calcium-calmodulin-dependent-protein-kinase-iv
#10
Huma Naz, Parvez Khan, Mohd Tarique, Safikur Rahman, Abha Meena, Shahzaib Ahamad, Suaib Luqman, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human calcium/calmodulin-dependent protein kinase IV (CAMKIV), a member of Ser/Thr kinase family, is associated with cancer, cerebral hypoxia and neurodegenerative diseases. β-carotene is a colored organic compound, abundant in plants and fruits and is used in cancer prevention. Here, we report a strong binding affinity of β-carotene with CAMKIV using molecular docking, fluorescence binding and isothermal titration calorimetry methods. Furthermore, β-carotene also reduces the enzyme activity of CAMKIV moderately as observed during ATPase assay...
December 9, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#11
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27895315/identification-of-aberrantly-expressed-glycans-in-gastric-cancer-by-integrated-lectin-microarray-and-mass-spectrometric-analyses
#12
Xiang Li, Feng Guan, Dongliang Li, Zengqi Tan, Ganglong Yang, Yanli Wu, Zhaohui Huang
Cancer progression is usually associated with alterations of glycan expression patterns. Little is known regarding global glycomics in gastric cancer, the most common type of epithelial cancer. We integrated lectin microarray and mass spectrometry (MS) methods to profile glycan expression in three gastric cancer cell lines (SGC-7901, HGC-27, and MGC-803) and one normal gastric epithelial cell line (GES-1). Significantly altered glycans were confirmed by lectin staining and MALDI-TOF/TOF-MS. The three cancer cell lines showed increased levels of core-fucosylated N-glycans, GalNAcα-Ser/Thr (Tn antigen), and Sia2-6Galβ1-4GlcNAc N-glycans, but reduced levels of biantennary N-glycans, Galβ1-3GalNAcα-Ser/Thr (T antigen), and (GlcNAc)n N-glycans...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889995/the-roles-of-the-unique-prolyl-isomerase-pin1-in-cancer-related-viral-and-bacterial-infections
#13
J Wang, X-H Liao, M Zheng, D Yang, X Z Zhou, H Liu, K P Lu
Infection is the process of pathogen invasion, as well as the host reaction to the foreign agents. Proline-directed phosphorylation is a major regulatory mechanism that regulates the function of fundamental proteins involved in infection and infection-induced cancer. Recently, the identification of the phosphorylation-dependent prolyl isomerase Pin1 has uncovered a unique regulatory signaling mechanism controlling protein conformation and function after phosphorylation. Pin1 is the only proline isomerase that specifically recognizes certain Pro-directed Ser/Thr phosphorylation motifs...
November 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27871003/magnetic-mesoporous-nanospheres-anchored-with-lyp-1-as-an-efficient-pancreatic-cancer-probe
#14
Yongjian Jiang, Shaojun Liu, Yu Zhang, Hengchao Li, Hang He, Juntao Dai, Tao Jiang, Weihang Ji, Daoying Geng, Ahmed A Elzatahry, Abdulaziz Alghamdi, Deliang Fu, Yonghui Deng, Dongyuan Zhao
Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27861885/sensitivity-of-tp53-mutated-cancer-cells-to-the-phytoestrogen-genistein-is-associated-with-direct-inhibition-of-plk1-activity
#15
Sol-Bi Shin, Sang-Uk Woo, Young Won Chin, Young-Joo Jang, Hyungshin Yim
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR...
November 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27856640/g-protein-coupled-receptors-gpcrs-that-signal-via-protein-kinase-a-pka-cross-talk-at-insulin-receptor-substrate-1-irs1-to-activate-the-phosphatidylinositol-3-kinase-pi3k-akt-pathway
#16
Nathan C Law, Morris F White, Mary E Hunzicker-Dunn
G protein-coupled receptors (GPCRs) activate PI3K/v-AKT thymoma viral oncoprotein (AKT) to regulate many cellular functions that promote cell survival, proliferation, and growth. However, the mechanism by which GPCRs activate PI3K/AKT remains poorly understood. We used ovarian preantral granulosa cells (GCs) to elucidate the mechanism by which the GPCR agonist FSH via PKA activates the PI3K/AKT cascade. Insulin-like growth factor 1 (IGF1) is secreted in an autocrine/paracrine manner by GCs and activates the IGF1 receptor (IGF1R) but, in the absence of FSH, fails to stimulate YXXM phosphorylation of IRS1 (insulin receptor substrate 1) required for PI3K/AKT activation...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27809417/design-synthesis-and-biological-evaluation-of-pyrimidine-derivatives-as-potential-inhibitors-of-human-calcium-calmodulin-dependent-protein-kinase-iv
#17
Ehtesham Jameel, Huma Naz, Parvez Khan, Mohd Tarique, Jitendra Kumar, Syed Mumtazuddin, Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Nasimul Hoda, Md Imtaiyaz Hassan
Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a multifunctional Ser/Thr kinase, associated with cerebral hypoxia, cancer, and neurodegenerative diseases. Here, we report design, synthesis, and biological evaluation of seven pyrimidine-substituted novel inhibitors of CAMKIV. We successfully synthesized and extensively characterized (ESI-MS, (1) H NMR, and (13) C NMR studies) seven compounds that are showing appreciable binding affinity to the CAMKIV. Molecular docking and fluorescence binding studies revealed that compound 1 is showing very high binding free energy (ΔG = -11...
November 3, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27787230/integrated-in-silico-in-vitro-characterization-identification-and-disruption-of-the-intermolecular-interaction-between-sh3-domain-containing-protein-kinases-and-human-pituitary-tumor-transforming-gene-1
#18
Yanan Li, Mengmeng Li, Weijie Min, Guosheng Han, Laixing Wang, Chao Chen, Zifu Li, Yuhui Zhang, Jianmin Li, Zhijian Yue
The human pituitary tumor-transforming gene-1 (hPTTG1) has been found to be overexpressed in various cancers. Accumulated evidences implicate that some of protein kinases can specifically recognize two PXXP motifs at hPTTG1 C-terminus through their Src homology (SH3) domain and then phosphorylate the protein by their catalytic domain. Here, we integrate in silico analysis and in vitro assay to characterize the intermolecular interaction between the two hPTTG1 motif peptides 161LGPPSPVK168 (M1P) and 168KMPSPPWE175 (M2P) and the SH3 domains of Ser/Thr-specific protein kinases MAP3K and PI3K...
January 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27769050/protein-phosphatase-mg2-mn2-dependent-1f-promotes-smoking-induced-breast-cancer-by-inactivating-phosphorylated-p53-induced-signals
#19
Shih-Hsin Tu, Yin-Ching Lin, Chi-Cheng Huang, Po-Sheng Yang, Hui-Wen Chang, Chien-Hsi Chang, Chih-Hsiung Wu, Li-Ching Chen, Yuan-Soon Ho
We previously demonstrated that the activation of α9-nicotinic acetylcholine receptor (α9-nAchR) signaling by smoking promotes breast cancer formation. To investigate the downstream signaling molecules involved in α9-nAChR-induced breast tumorigenesis, we used real-time polymerase chain reactions and Western blotting to assess expression of protein phosphatase Mg2+/Mn2+ dependent 1F (PPM1F), a Ser/Thr protein phosphatase, in human breast cancer samples (n=167). Additionally, stable PPM1F-knockdown and -overexpressing cell lines were established to evaluate the function of PPM1F...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27768322/a-redox-sensitive-and-rage-targeting-nanocarrier-for-hepatocellular-carcinoma-therapy
#20
Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
November 7, 2016: Molecular Pharmaceutics
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