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https://www.readbyqxmd.com/read/28804913/on-bh3-mimetics-and-ca-2-signaling
#1
Pawel E Ferdek, Monika A Jakubowska
Preclinical Research BH3 mimetics are anticancer agents that reproduce the spatial arrangement of the BH3 domain of Bcl-2 family proteins. Just like the BH3-only proteins, these compounds bind to the hydrophobic cleft of the pro-survival Bcl-2 members such as Bcl-2 or Bcl-xL, and disrupt their heterodimerization with pro-apoptotic Bax or Bak, sensitizing cells to chemotherapy. In recent years, it has become clear that Bcl-2 family proteins are engaged in regulation of intracellular Ca(2+) homeostasis, including Ca(2+) release from the intracellular stores as well as Ca(2+) fluxes across the plasma membrane...
August 13, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28802125/novel-4-3-4-oxo-5-2-oxoindolin-3-ylidene-thiazolidin-2-ylidene-amino-benzenesulfonamides-synthesis-carbonic-anhydrase-inhibitory-activity-anticancer-activity-and-molecular-modelling-studies
#2
Wagdy M Eldehna, Mahmoud F Abo-Ashour, Alessio Nocentini, Paola Gratteri, Ibrahim H Eissa, Mohamed Fares, Omnia E Ismael, Hazem A Ghabbour, Mahmoud M Elaasser, Hatem A Abdel-Aziz, Claudiu T Supuran
Herein we report the synthesis of two series of novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino)benzenesulfonamides (4a-m and 7a-g). All the newly prepared sulfonamides were in vitro investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IV and IX, using a stopped-flow CO2 hydrase assay. In particular, hCA isoforms II and IX (tumor-associated) were more susceptible to inhibition by the synthesized derivatives, with KIs in the range of 2...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28801714/parthenolide-attenuates-7-12-dimethylbenz-a-anthracene-induced-hamster-buccal-pouch-carcinogenesis
#3
Nagarethinam Baskaran, Govindan Sadasivam Selvam, Subramani Yuvaraj, Albert Abhishek
Over the decades, the survival rates for oral cancer have not improved despite development in novel diagnostic and therapeutic strategies. Therefore, the present study is aimed at investigating the chemopreventive potential of parthenolide in DMBA-induced hamster buccal pouch carcinogenesis. The hamsters were divided into 4 groups (n = 6/group). Group I was treated as control. Groups II and III were painted with a solution of 0.5% DMBA three times per week for 14 weeks on the left buccal pouches. In addition, group III were orally administrated with parthenolide 2 mg/kg b...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28801605/luteolin-a-natural-flavonoid-inhibits-methylglyoxal-induced-apoptosis-via-the-mtor-4e-bp1-signaling-pathway
#4
Yi Liu, Jie Huang, Xian Zheng, Xia Yang, Yan Ding, Tongyong Fang, Yuyun Zhang, Shuaishuai Wang, Xiaofei Zhang, Xuan Luo, Anlei Guo, Kelly A Newell, Yinghua Yu, Xu-Feng Huang
Methylglyoxal (MG) accumulation has been observed in human cerebrospinal fluid and body tissues under hyperglycaemic conditions. Recent research has demonstrated that MG-induces neuronal cell apoptosis, which promotes the development of diabetic encephalopathy. Our previous animal study has shown that luteolin, a natural flavonoid, attenuates diabetes-associated cognitive dysfunction. To further explore the neuroprotective properties of luteolin, we investigated the inhibitive effect of luteolin on MG-induced apoptosis in PC12 neuronal cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800142/alcohol-mediated-missplicing-of-mcl-1-pre-mrna-is-involved-in-neurotoxicity
#5
Rahsan Sariyer, Francesca I De Simone, Martina Donadoni, Jan B Hoek, Sulie L Chang, Ilker Kudret Sariyer
BACKGROUND: Heavy and chronic ethanol (EtOH) exposure can cause significant structural and functional damage to the adult brain. The most devastating consequence of EtOH exposure is the neurotoxicity associated with the depletion of neurons. Regulation of splice variants in the brain can modulate protein functions, which may ultimately affect behaviors associated with alcohol dependence and EtOH-mediated neurotoxicity. Since alcohol consumption is associated with neurotoxicity, it is possible that altered splicing of survival and pro-survival factors during the development of alcoholism may contribute to the neurotoxicity...
August 11, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28797724/the-effect-of-newly-synthesized-progesterone-derivatives-on-apoptotic-and-angiogenic-pathway-in-mcf-7-breast-cancer-cells
#6
Shaymaa M M Yahya, Abdou O Abdelhamid, Mervat M Abd-Elhalim, Ghada H Elsayed, Emad F Eskander
Due to its high potency and selectivity, anticancer agents consisting of combined molecules have gained great interests. The current study introduces newly synthesized progesterone derivatives of promising anticancer effect. Moreover, the pro-apoptotic and anti-angiogenic effects of these compounds were studied extensively. Several thiazole, pyridine, pyrazole, thiazolopyridine and pyrazolopyridine progesterone derivatives were synthesized. The structure of the novel progesterone derivatives was elucidated and confirmed using the analytical and spectral data...
August 8, 2017: Steroids
https://www.readbyqxmd.com/read/28795692/the-novel-resveratrol-derivative-3-5-diethoxy-3-4-dihydroxy-trans-stilbene-induces-mitochondrial-ros-mediated-er-stress-and-cell-death-in-human-hepatoma-cells-in-vitro
#7
Jae-Woo Park, Woo-Gyun Choi, Phil-Jun Lee, Su-Wol Chung, Byung-Sam Kim, Hun-Taeg Chung, Sungchan Cho, Jong-Heon Kim, Byoung-Heon Kang, Hyoungsu Kim, Hong-Pyo Kim, Sung-Hoon Back
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells in vitro. Res-006 was more effectively suppressed the viability of HepG2 human hepatoma cells than resveratrol (the IC50 values were 67.2 and 354...
August 10, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28795302/novel-combination-of-2-methoxyestradiol-and-cyclophosphamide-enhances-the-antineoplastic-and-pro-apoptotic-effects-on-s-180-ascitic-tumour-cells
#8
Srabantika Mallick, Atish Barua, Goutam Paul, Samarendra Nath Banerjee
Sarcoma 180 (S-180) tumour cell line is a stable murine tumour cell line with 98-99% stumour takes capacity in Swiss albino mouse - Mus musculus. 2 Methoxyestradiol (2ME) - a promising anti-neoplastic and anti-angiogenic agent, showed toxicity to host body in higher concentration. Cyclophosphamide (CP), the anti-neoplastic agent has long been used as a chemotherapeutic drug for treatment of different cancers. Our studies have shown that the combination effect of 2ME and CP on S-180 tumour cell line is anti-proliferative and less toxic...
August 10, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28793310/reduced-internalization-of-tnf-%C3%A9-tnfr1-down-regulates-caspase-dependent-phagocytosis-induced-cell-death-picd-in-neonatal-monocytes
#9
Stephan Dreschers, Christian Gille, Martin Haas, Florence Seubert, Christopher Platen, Thorsten W Orlikowsky
Phagocytosis-induced cell death (PICD) is diminished in cord blood monocytes (CBMO) as compared to cells from adults (PBMO) due to differences in the CD95-pathway. This may support a prolonged pro-inflammatory response with sequels of sustained inflammation as seen in neonatal sepsis. Here we hypothesized that TNF-α mediated induction of apoptosis is impaired in CBMO due to differences in the TNFR1-dependent internalization. Monocytes were infected with Escherichia coli-GFP (E. coli-GFP). Monocyte phenotype, phagocytic activity, induction of apoptosis, and TNF-α/TNF-receptor (TNFR) -expression were analysed...
2017: PloS One
https://www.readbyqxmd.com/read/28792534/primary-bovine-skeletal-muscle-cells-enters-apoptosis-rapidly-via-the-intrinsic-pathway-when-available-oxygen-is-removed
#10
Sissel Beate Rønning, Petter Vejle Andersen, Mona Elisabeth Pedersen, Kristin Hollung
Muscle cells undergo changes post-mortem during the process of converting muscle into meat, and this complex process is far from revealed. Recent reports have suggested programmed cell death (apoptosis) to be important in the very early period of converting muscle into meat. The dynamic balance that occurs between anti-apoptotic members, such as Bcl-2, and pro-apoptotic members (Bid, Bim) helps determine whether the cell initiates apoptosis. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to investigate if apoptosis is induced when oxygen is removed from the growth medium...
2017: PloS One
https://www.readbyqxmd.com/read/28791439/metabolic-crosstalk-between-fatty-pancreas-and-fatty-liver-effects-on-local-inflammation-and-insulin-secretion
#11
Felicia Gerst, Robert Wagner, Gabriele Kaiser, Madhura Panse, Martin Heni, Jürgen Machann, Malte N Bongers, Tina Sartorius, Bence Sipos, Falko Fend, Christian Thiel, Silvio Nadalin, Alfred Königsrainer, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Susanne Ullrich, Dorothea Siegel-Axel
AIMS/HYPOTHESIS: Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. METHODS: Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68...
August 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28790362/double-stranded-rna-induces-chicken-t-cell-lymphoma-apoptosis-by-trif-and-nf-%C3%AE%C2%BAb
#12
Haitao Zou, Ruixue Su, Jing Ruan, Hongxia Shao, Kun Qian, Jianqiang Ye, Yongxiu Yao, Venugopal Nair, Aijian Qin
Toll-like receptor-3 (TLR3), a member of the pathogen recognition receptor family, has been reported to activate immune response and to exhibit pro-apoptotic activity against some tumor cells. However it is unclear whether TLR3 has same function against chicken lymphoma. In this paper we investigated the effect of TLR3 activation on a Marek's disease lymphoma-derived chicken cell line, MDCC-MSB1. The TLR3 agonist poly (I:C) activated TLR3 pathway and inhibited tumor cells proliferation through caspase-dependent apoptosis...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783582/cytotoxic-effects-of-fritillaria-imperialis-l-extracts-on-human-liver-cancer-cells-breast-cancer-cells-and-fibroblast-like-cells
#13
Ozra Zarei, Mohammad Mehdi Yaghoobi
In this study, we evaluated the cytotoxic effects of Fritillaria imperialis L. aqueous and ethanolic extracts on human liver cancer cells (LCL-PI 11), breast adenocarcinoma cells (MCF-7) and fibroblast-like cells (HSkMC). MTT, BrdU and TUNEL assays were used to detect cytotoxicity, proliferation rate and apoptotic death. Following 48h, the IC50 values for LCL-PI11 and MCF-7 cells were 4.2 and 3.9μg/mL of aqueous extract, and 1.7 and 1.3μg/mL of ethanolic extract, respectively, which was comparable to that of 5-FU...
August 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28782832/aav-delivery-of-grp78-bip-promotes-adaptation-of-human-rpe-cell-to-er-stress
#14
Shima Ghaderi, Shahin Ahmadian, Zahra-Soheila Soheili, Hamid Ahmadieh, Shahram Samiei, Samira Kheitan, Ehsan Ranaei Pirmardan
Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration...
August 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28782643/downregulation-of-trb3-protects-neurons-against-apoptosis-induced-by-global-cerebral-ischemia-and-reperfusion-injury-in-rats
#15
Kai Wei, Li Wan, Jin Liu, Bo Zhang, Xuan Li, Yue Zhang, Chuanhan Zhang, Wenlong Yao
Global cerebral ischemia and reperfusion injury (GCI/R) can lead to neuronal apoptosis and contributes to permanent neurological sequelae. However, the underlying mechanism is largely unknown. Therefore, the present study aimed to assess the effects of GCI/R on the tribbles homolog 3 (TRB3) and to explore the role of TRB3 in GCI/R. The GCI/R model was developed in Sprague-Dawley male rats by four-vessel occlusion. Subsequently, the expressions of TRB3, endoplasmic reticulum stress markers, and apoptosis-associated proteins were examined by western blot at 1h, 6h, 12h, 24h, and 72h after GCI/R...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#16
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28778086/connective-tissue-growth-factor-mediates-tgf-%C3%AE-1-induced-low-grade-serous-ovarian-tumor-cell-apoptosis
#17
Jung-Chien Cheng, Hsun-Ming Chang, Peter C K Leung
Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28778072/bid-deficient-fish-delay-grass-carp-reovirus-gcrv-replication-and-attenuate-gcrv-triggered-apoptosis
#18
Libo He, Hao Wang, Lifei Luo, Yongming Li, Rong Huang, Lanjie Liao, Zuoyan Zhu, Yaping Wang
Bid, BH3-interacting domain death agonist, is a pro-apoptotic BH3-only member of Bcl-2 family, playing an important role in apoptosis. In the study, Bid genes from grass carp (Ctenopharyngodon idellus) and rare minnow (Gobiocypris rarus), named CiBid and GrBid, were cloned and analyzed. Bid was constitutively expressed in all examined tissues of grass carp, but the expression level varied in different tissues. Following grass carp reovirus (GCRV) stimulation in vivo, Bid and apoptosis related genes Caspase-9 and Caspase-3 was up-regulated significantly at the late stage of infection...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28777518/a-single-air-dive-induces-apoptotic-gene-regulation-but-no-increase-in-nucleosomes
#19
Lars Eichhorn, Christian Nietzel, Stefan Schröder, Ullrich Siekmann, Andreas Koch, Stefan Weber
BACKGROUND: Oxidative stress caused by elevated partial pressure of oxygen during diving is a major contributor of inflammation and apoptosis. The underlying molecular mechanisms are poorly understood. The aim of the study was to describe apoptotic gene regulation induced by a single air dive. METHODS: 19 healthy volunteers were exposed to a 30-minute dive at 2.8 atmospheres (ATA) absolute in a pressure chamber in ambient air. Blood samples were obtained before, directly after and 24 hours after exposure...
November 2016: Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc
https://www.readbyqxmd.com/read/28777375/inhibition-of-bcl-xl-prevents-pro-death-actions-of-%C3%AE-n-bcl-xl-at-the-mitochondrial-inner-membrane-during-glutamate-excitotoxicity
#20
Han-A Park, Pawel Licznerski, Nelli Mnatsakanyan, Yulong Niu, Silvio Sacchetti, Jing Wu, Brian M Polster, Kambiz N Alavian, Elizabeth A Jonas
ABT-737 is a pharmacological inhibitor of the anti-apoptotic activity of B-cell lymphoma-extra large (Bcl-xL) protein; it promotes apoptosis of cancer cells by occupying the BH3-binding pocket. We have shown previously that ABT-737 lowers cell metabolic efficiency by inhibiting ATP synthase activity. However, we also found that ABT-737 protects rodent brain from ischemic injury in vivo by inhibiting formation of the pro-apoptotic, cleaved form of Bcl-xL, ΔN-Bcl-xL. We now report that a high concentration of ABT-737 (1 μM), or a more selective Bcl-xL inhibitor WEHI-539 (5 μM) enhances glutamate-induced neurotoxicity while a low concentration of ABT-737 (10 nM) or WEHI-539 (10 nM) is neuroprotective...
August 4, 2017: Cell Death and Differentiation
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