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https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#1
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341114/recombinant-human-hepatocyte-growth-factor-provides-protective-effects-in-celurein-induced-acute-pancreatitis-in-mice
#2
Mayrel Palestino-Domínguez, Mario Pelaez-Luna, Roberto Lazzarini-Lechuga, Ignacio Rodríguez-Ochoa, Verónica Souza, Roxana U Miranda, Benjamín Pérez-Aguilar, Leticia Bucio, Jens U Marquardt, Luis Enrique Gomez-Quiroz, María Concepción Gutiérrez-Ruiz
Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c-Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein-induced acute pancreatitis...
January 17, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29340361/a-curcumin-loaded-polymeric-micelle-as-a-carrier-of-a-microrna-21-antisense-oligonucleotide-for-enhanced-anti-tumor-effects-in-a-glioblastoma-animal-model
#3
Xiaonan Tan, Gyeungyun Kim, Dahee Lee, Jungju Oh, Minkyung Kim, Chunxian Piao, Jaewon Lee, Min Sang Lee, Ji Hoon Jeong, Minhyung Lee
A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and miR21ASO...
January 17, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29340085/6-methylsulfonyl-hexyl-isothiocyanate-as-potential-chemopreventive-agent-molecular-and-cellular-profile-in-leukaemia-cell-lines
#4
Monia Lenzi, Veronica Cocchi, Marco Malaguti, Maria Cristina Barbalace, Silvia Marchionni, Silvana Hrelia, Patrizia Hrelia
Numerous laboratory and epidemiological studies show that the risk of developing several types of cancer can be reduced with the employment of natural substances that act with multiple mechanisms. In this context, an important role is played by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC), present in the root of Wasabia Japonica, has stimulated the interest of researchers as a chemopreventive agent. In this particular study we have focused on evaluating 6-MITC's in vitro cytotoxic, cytostatic and cytodifferentiating activities, as well as its pro-apoptotic potential...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340082/reciprocal-sensitivity-of-diffuse-large-b-cell-lymphoma-cells-to-bcl-2-inhibitors-bird-2-versus-venetoclax
#5
Tamara Vervloessem, Haidar Akl, Thomas Tousseyn, Humbert De Smedt, Jan B Parys, Geert Bultynck
Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some cancers with elevated Bcl-2 display poor responses towards BH3 mimetics, suggesting an additional function for anti-apoptotic Bcl-2 in these cancers. Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5-trisphosphate receptor (IP3R)...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340081/pcpa-protects-against-monocrotaline-induced-pulmonary-arterial-remodeling-in-rats-potential-roles-of-connective-tissue-growth-factor
#6
Yang Bai, Zhong-Xia Li, Yue-Tong Zhao, Mo Liu, Yun Wang, Guo-Chao Lian, Qi Zhao, Huai-Liang Wang
The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP), right ventricle hypertrophy index (RVI) and pulmonary artery morphology were assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by western blot or immunohistochemistry...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339102/spirulina-ameliorates-methotrexate-hepatotoxicity-via-antioxidant-immune-stimulation-and-proinflammatory-cytokines-and-apoptotic-proteins-modulation
#7
Asmaa F Khafaga, Yasser S El-Sayed
AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, MTX (20 mg/kg bwt, single ip injection), SP (500 mg/kg bwt, oral gavage daily for 21 days), and MTX+SP...
January 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29339024/nrf2-are-pathway-attenuates-oxidative-and-apoptotic-response-in-human-osteoarthritis-chondrocytes-by-activating-erk1-2-elk1-p70s6k-p90rsk-signaling-axis
#8
Nazir M Khan, Imran Ahmad, Tariq M Haqqi
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1β stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient...
January 12, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29337363/inhibition-of-apoptosis-using-exosomes-in-chinese-hamster-ovary-cell-culture
#9
Seora Han, Won Jong Rhee
Animal cell culture technology for therapeutic protein production has shown significant improvement over the last few decades. Chinese hamster ovary (CHO) cells have been widely adapted for the production of biopharmaceutical drugs. In the biopharmaceutical industry, it is crucial to develop cell culture media and culturing conditions to achieve the highest productivity and quality. However, CHO cells are significantly affected by apoptosis in the bioreactors, resulting in a substantial decrease in product quantity and quality...
January 16, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29337231/apoptosis-induction-by-pleurotus-sajor-caju-fr-singer-extracts-on-colorectal-cancer-cell-lines
#10
Tiane C Finimundy, Rui M V Abreu, Natalia Bonetto, Fernando J Scariot, Aldo J P Dillon, Sergio Echeverrigaray, Lillian Barros, Isabel C F R Ferreira, João A P Henriques, Mariana Roesch-Ely
Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116wt cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC50 value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation...
January 11, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29336479/inhibition-of-glycolytic-metabolism-in-glioblastoma-cells-by-pt3glc-combinated-with-pi3k-inhibitor-via-sirt3-mediated-mitochondrial-and-pi3k-akt-mapk-pathway
#11
Gang Wang, Xing-Li Fu, Jun-Jie Wang, Rui Guan, Yan Sun, Shing-Shun Tony To
Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with abnormal expression of genes that mediate glycolytic metabolism and tumor cell growth. Petunidin-3-O- glucoside (Pt3glc) is a kind of anthocyanin in the red grape and derived beverages, representing the most common naturally occurring anthocyanins with a reduced incidence of cancer and heart diseases. In this study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell was investigated by using the DBTRG-05MG cell lines...
January 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29336118/resveratrol-potently-counteracts-quercetin-starvation-induced-autophagy-and-sensitizes-hepg2-cancer-cells-to-apoptosis
#12
Sarah Tomas-Hernández, Jordi Blanco, Cristina Rojas, Joel Roca-Martínez, María José Ojeda-Montes, Raúl Beltrán-Debón, Santiago Garcia-Vallve, Gerard Pujadas, Lluís Arola, Miquel Mulero
SCOPE: Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29335519/metabolic-reprogramming-by-pck1-promotes-tca-cataplerosis-oxidative-stress-and-apoptosis-in-liver-cancer-cells-and-suppresses-hepatocellular-carcinoma
#13
Meng-Xi Liu, Lei Jin, Si-Jia Sun, Peng Liu, Xu Feng, Zhou-Li Cheng, Wei-Ren Liu, Kun-Liang Guan, Ying-Hong Shi, Hai-Xin Yuan, Yue Xiong
Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29334666/effects-of-berberine-chloride-on-the-liver-of-streptozotocin-induced-diabetes-in-albino-wistar-rats
#14
Govindasami Chandirasegaran, Chakkaravarthy Elanchezhiyan, Kavisa Ghosh
The goal of the present study is to evaluate the effect of Berberine chloride (BC) on the liver of streptozotocin (STZ) induced diabetic rat. Diabetic rats were treated with BC (50 mg/kg b.w) or glibenclamide (6 mg/kg b.w), daily for 45 days. After BC treatment in diabetic rats, there was a significant (P < 0.05) decline in the levels of hepatic markers, lipid peroxidation markers such as lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS), and pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor kappa-B-p65 (phospho-NF-κB p65), cyclooxygenase (COX-2), nitric oxide synthase (iNOS) as well as pro-apoptotic mediators such as Bax and cytochrome c...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334254/antioxidant-and-anti-proliferative-properties-of-extracts-from-heterotrophic-cultures-of-galdieria-sulphuraria
#15
Claudia Bottone, Rosa Camerlingo, Roberta Miceli, Giovanna Salbitani, Giuseppe Sessa, Giuseppe Pirozzi, Simona Carfagna
This study explores the possibility to use the extremophilic microalga Galdieria sulphuraria (strain 064) as a source of natural biomolecules with beneficial and protective effects on human health. Galdieria was cultivated in heterotrophy conditions and cells extracts for their antioxidant and anti-proliferative properties were tested. Galdieria extracts showed high antioxidant power tested through ABTS assay and revealed high glutathione and phycocyanin contents. Based on Annexin-V FITC/propidium iodide and MTT analysis, algae extracts inhibited the proliferation of human adenocarcinoma A549 cells (51...
January 15, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29330691/bis-guanylhydrazones-as-efficient-anti-candida-compounds-through-dna-interaction
#16
Jelena Lazić, Vladimir Ajdačić, Sandra Vojnovic, Mario Zlatović, Marina Pekmezovic, Selene Mogavero, Igor Opsenica, Jasmina Nikodinovic-Runic
Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone- and guanidine-containing molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C...
January 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29330285/foxo-dependent-par-4-upregulation-prevents-long-term-survival-of-residual-cells-following-pi3k-akt-inhibition
#17
Jeffrey S Damrauer, Stephanie N Phelps, Katie Amuchastegui, Ryan Lupo, Nathaniel W Mabe, Andrea Walens, Benjamin R Kroger, James V Alvarez
Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathways that regulate residual cancer cell survival may suggest opportunities for targeting these cells to prevent recurrence. Previously it was observed that the pro-apoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330151/interleukin-22-reverses-human-islet-dysfunction-and-apoptosis-triggered-by-hyperglycemia-and-light
#18
Shadab Abadpour, Bente Halvorsen, Afaf Sahraoui, Olle Korsgren, Pål Aukrust, Hanne Scholz
Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22...
January 12, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29328470/cobalt-protoporphyrin-enhances-heme-oxygenase-1-expression-and-attenuates-liver-ischemia-reperfusion-injury-by-inhibiting-apoptosis
#19
Jing Li, Bin Wu, Dahong Teng, Xiaoye Sun, Junjie Li, Jiang Li, Guoliang Zhang, Jinzhen Cai
The aim of the present study was to investigate the preconditioning effect and underlying mechanisms of cobalt-protoporphyrin (CoPP) in a mouse model of liver ischemia‑reperfusion (I/R) injury. Mice were divided into five groups: Sham‑operated (control), I/R, I/R + CoPP, I/R + CoPP and zinc‑protoporphyrin (ZnPP) and I/R + ZnPP. Serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) were detected using commercial kits. The expression of the pro‑apoptotic protein caspase‑3 was detected by immunohistochemistry and the expression levels of the anti‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) and heme oxygenase 1 (HO‑1) were analyzed by western blotting...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328387/rhus-verniciflua-stokes-extract-induces-inhibition-of-cell-growth-and-apoptosis-in-human-chronic-myelogenous-leukemia-k562-cells
#20
Kyung-Wook Lee, Eun-Sik Um, Bo-Bae Jung, Eun-Sol Choi, Eun-Young Kim, Seungbo Lee, Eungyeong Jang, Jang-Hoon Lee, Youngchul Kim
Rhus verniciflua Stokes has been widely used as a traditional medicinal plant with a variety of pharmacological activities. We investigated the mechanisms involved in mediating the effects of Rhus verniciflua Strokes (R. verniciflua) extract in human chronic myelogenous leukemia K562 cells, including caspase-dependent apoptotic pathways related to cell-cycle arrest, as well as the inhibition of nuclear factor NF-κB activation and upregulation of the mitogen-activated protein kinase (MAPK) signaling pathway...
January 3, 2018: Oncology Reports
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