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https://www.readbyqxmd.com/read/28214890/a-new-perspective-for-osteosarcoma-therapy-proteasome-inhibition-by-mln9708-2238-successfully-induces-apoptosis-and-cell-cycle-arrest-and-attenuates-the-invasion-ability-of-osteosarcoma-cells-in-vitro
#1
Renhao Liu, Chunjiang Fu, Jiabing Sun, Xvming Wang, Shuo Geng, Xiaoyu Wang, Jilong Zou, Zhenggang Bi, Chenglin Yang
BACKGROUND: The proteasome exists in all eukaryotic cells and provides the main route of intracellular proteins degradation involved in cell growth and apoptosis. Proteasome inhibition could block protein degradation pathways and disturb regulatory networks, possibly leading to profound effects on cell growth, particularly in cancer cells. A proteasome inhibitor with an appropriate toxicity index for malignant cells rather than normal cells would be an attractive anticancer therapy. METHODS: The human osteosarcoma (OS) cell lines MG-63 and Saos-2 and normal osteoblast cells were used to study the antitumour activity of the proteasome inhibitor MLN9708/2238...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214549/atp-dependent-activity-and-mitochondrial-localization-of-drug-efflux-pumps-in-doxorubicin-resistant-breast-cancer-cells
#2
Julie Dartier, Elsa Lemaitre, Igor Chourpa, Caroline Goupille, Stéphane Servais, Stéphan Chevalier, Karine Mahéo, Jean-François Dumas
BACKGROUND: We hypothesized that, among the mechanisms of drug-resistance acquired by doxorubicin (DOX)-resistant breast cancer cells to maintain cell survival, ATP-dependent drug efflux pumps could be expressed in their mitochondrial membranes and this might limit the accumulation of DOX in this subcellular compartment in relation to mitochondrial ATP production. Methods/results Mitochondrial DOX accumulation: the presence and the activity of mitochondrial efflux pumps and their relationship with mitochondrial ATP synthesis were analyzed in DOX-resistant (MCF-7dox(R)) and -sensitive (MCF-7(S)) breast cancer cells...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214344/neferine-potentiates-the-antitumor-effect-of-cisplatin-in-human-lung-adenocarcinoma-cells-via-a-mitochondria-mediated-apoptosis-pathway
#3
Kalai Selvi Sivalingam, Poornima Paramasivan, Ching Feng Weng, Viswanadha Vijaya Padma
Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G0/G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes as well as loss of mitochondrial membrane potential (ΔΨM)...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214294/ptk6-localized-at-the-plasma-membrane-promotes-cell-proliferation-and-migration-through-phosphorylation-of-eps8
#4
Won-Sik Shin, Hyun Jae Shim, Young Hun Lee, Minju Pyo, Jun Sang Park, So Yun Ahn, Seung-Taek Lee
Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma-membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214283/prognostic-role-of-n-cadherin-expression-in-patients-with-non-muscle-invasive-bladder-cancer
#5
Mohammad Abufaraj, Shahrokh F Shariat, Andrea Haitel, Marco Moschini, Beat Foerster, Piotr Chłosta, Kilian Gust, Marek Babjuk, Alberto Briganti, Pierre I Karakiewicz, Walter Albrecht
PURPOSE: To assess the role of N-cadherin as a prognostic biomarker in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection with or without adjuvant intravesical therapy. PATIENTS AND METHODS: Immunohistochemistry using monoclonal mouse antibody was used to evaluate the expression status of N-cadherin in 827 patients with NMIBC. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected...
February 14, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#6
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213961/chrysin-induces-death-of-prostate-cancer-cells-by-inducing-ros-and-er-stress
#7
Soomin Ryu, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Chrysin is a natural flavone found in numerous plant extracts, honey and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G1 phase of the cell cycle...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213729/alpha-tocopherol-transfer-protein-%C3%AE-ttp-is-expressed-in-endometrial-carcinoma-and-is-correlated-with-figo-stage-and-5-year-survival
#8
Sabine Heublein, Thomas Vrekoussis, Ronny Etzl, Daisy Rotzoll, Christina Kuhn, Gesine Faigle, Iordanis Navrozoglou, Theodore Stefos, Antonis Makrigiannakis, Udo Jeschke
BACKGROUND: Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer. MATERIALS AND METHODS: Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot...
February 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#9
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28213228/smartphone-based-immunosensor-for-ca125-detection
#10
Oana Hosu, Andrea Ravalli, Giuseppe Mattia Lo Piccolo, Cecilia Cristea, Robert Sandulescu, Giovanna Marrazza
In this work, we report the design, the development and the characterization of the analytical performances of a colorimetric smartphone-based immunosensor for the detection of cancer antigen 125 (CA125). The immunosensor was based on a sandwich strategy in which the primary antibody was immobilized by spotting onto the 3D nitrocellulose membrane. The immunospots were subsequently incubated with CA125 solutions, followed by the affinity reaction with a secondary antibody labeled with gold nanoparticles (AuNPs)...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28212843/natural-extranuclear-androgen-receptor-ligands-as-endocrine-disruptors-of-cancer-cell-growth
#11
Marilena Kampa, George Notas, Elias Castanas
Even though the term endocrine disruption primarily designates environmental chemicals that can interfere with the action of hormones, in recent years it has been extended to include also plant derived compounds that can reach the human body, naturally, or have been identified and studied as alternative pharmaceutical agents. In fact, for a large number of them, their antihormonal action was appreciated by different traditional herbal medicines. In the present review we report the majority of the plant derived compounds that exhibit an antiandrogenic effect and the known mechanisms of action...
February 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28212731/hamlet-a-protein-lipid-complex-with-broad-tumoricidal-activity
#12
REVIEW
James C S Ho, Aftab Nadeem, Catharina Svanborg
HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212713/rationally-designed-peptide-probes-for-extracellular-vesicles
#13
R Tamura, H Yin
Extracellular vesicles (EVs) are submicroscopic lipid vesicles secreted from cells and play significant roles in cell-to-cell communication by transporting varieties of cell signaling molecules like proteins, DNA, mRNA, and microRNA. Recent studies showed that EVs are highly correlated with cancer progression and metastasis. However, there are some difficulties in probing each vesicle using popular analytical methods because of their small sizes and heterogeneous origins. These obstacles may be overcome by using a novel approach that senses highly curved membrane and negatively charged membrane lipids...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28212423/phenolic-extract-from-oleaster-olea-europaea-var-sylvestris-leaves-reduces-colon-cancer-growth-and-induces-caspase-dependent-apoptosis-in-colon-cancer-cells-via-the-mitochondrial-apoptotic-pathway
#14
Wafa Zeriouh, Abdelhafid Nani, Meriem Belarbi, Adélie Dumont, Charlotte de Rosny, Ikram Aboura, Fatima Zahra Ghanemi, Babar Murtaza, Danish Patoli, Charles Thomas, Lionel Apetoh, Cédric Rébé, Dominique Delmas, Naim Akhtar Khan, François Ghiringhelli, Mickael Rialland, Aziz Hichami
Dietary polyphenols, derived from natural products, have received a great interest for their chemopreventive properties against cancer. In this study, we investigated the effects of phenolic extract of the oleaster leaves (PEOL) on tumor growth in mouse model and on cell death in colon cancer cell lines. We assessed the effect of oleaster leaf infusion on HCT116 (human colon cancer cell line) xenograft growth in athymic nude mice. We observed that oleaster leaf polyphenol-rich infusion limited HCT116 tumor growth in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28211613/novel-anticarcinoembryonic-antigen-antibody-drug-conjugate-has-antitumor-activity-in-the-existence-of-soluble-antigen
#15
Daisuke Shinmi, Ryosuke Nakano, Keisuke Mitamura, Minami Suzuki-Imaizumi, Junko Iwano, Yuya Isoda, Junichi Enokizono, Yasuhisa Shiraishi, Emi Arakawa, Kazuma Tomizuka, Kazuhiro Masuda
Carcinoembryonic antigen (CEA) is a classic tumor-specific antigen that is overexpressed in several cancers, including gastric cancer. Although some anti-CEA antibodies have been tested, to the best of our knowledge, there are currently no clinically approved anti-CEA antibody therapies. Because of this, we have created the novel anti-CEA antibody, 15-1-32, which exhibits stronger binding to membrane-bound CEA on cancer cells than existing anti-CEA antibodies. 15-1-32 also shows poor affinity for soluble CEA; thus, the binding activity of 15-1-32 to membrane-bound CEA is not influenced by soluble CEA...
February 17, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28211573/the-cationic-small-molecule-gw4869-is-cytotoxic-to-high-phosphatidylserine-expressing-myeloma-cells
#16
Slavica Vuckovic, Kate Vandyke, David A Rickards, Padraig McCauley Winter, Simon H J Brown, Todd W Mitchell, Jun Liu, Jun Lu, Philip W Askenase, Elizabeth Yuriev, Ben Capuano, Paul A Ramsland, Geoffrey R Hill, Andrew C W Zannettino, Andrew T Hutchinson
We have discovered that a small cationic molecule, GW4869, is cytotoxic to a subset of myeloma cell lines and primary myeloma plasma cells. Biochemical analysis revealed that GW4869 binds to anionic phospholipids such as phosphatidylserine - a lipid normally confined to the intracellular side of the cell membrane. However, interestingly, phosphatidylserine was expressed on the surface of all myeloma cell lines tested (n = 12) and 9/15 primary myeloma samples. Notably, the level of phosphatidylserine expression correlated well with sensitivity to GW4869...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28209994/reversal-of-the-apoptotic-resistance-of-non-small-cell-lung-carcinoma-towards-trail-by-natural-product-toosendanin
#17
Xin Li, Ming You, Yong-Jian Liu, Lin Ma, Pei-Pei Jin, Ri Zhou, Zhao-Xin Zhang, Baojin Hua, Xiao-Jun Ji, Xiao-Ying Cheng, Fangzhou Yin, Yan Chen, Wu Yin
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209968/activating-akt1-mutations-alter-dna-double-strand-break-repair-and-radiosensitivity
#18
S Oeck, K Al-Refae, H Riffkin, G Wiel, R Handrick, D Klein, G Iliakis, V Jendrossek
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209803/correlation-between-membrane-protein-concentrations-and-transcellular-transport-activity-for-breast-cancer-resistance-protein
#19
Houfu Liu, Liang Huang, Yi Li, Tingting Fu, Xueying Sun, Yan-Yan Zhang, Ruina Gao, Qingfang Chen, Wandong Zhang, Jasminder Sahi, Scott Summerfield, Kelly Dong
Emerging evidence indicates an important role for breast cancer resistance protein (BCRP) in limiting brain penetration of substrate drugs. While in vitro Transwell® assays can provide an indication of BCRP substrate potential, the predictability of these to in vivo brain penetration is still under debate. The present study examines the correlation of BCRP protein concentration and transcellular transport activity across MDCKII monolayers. We expressed human BCRP or murine Bcrp1 in MDCKII wild-type cells using BacMam2 virus transduction...
February 16, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28208769/localisation-microscopy-of-breast-epithelial-erbb-2-receptors-and-gap-junctions-trafficking-after-%C3%AE-irradiation-neuregulin-1%C3%AE-and-trastuzumab-application
#20
Götz Pilarczyk, Ines Nesnidal, Manuel Gunkel, Margund Bach, Felix Bestvater, Michael Hausmann
In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion-a process attenuated by trastuzumab antibody application...
February 9, 2017: International Journal of Molecular Sciences
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