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Bcl-2 inhibitors

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https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#1
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522550/suppression-of-microrna-135b-5pprotects-againstmyocardial-ischemia-reperfusion-injury-by-activatingjak2-stat3-signaling-pathway-in-mice-duringsevofluraneanesthesia
#2
Xiao-Juan Xie, Dong-Mei Fan, Kai Xi, Ya-Wei Chen, Peng-Wei Qi, Qian-Hui Li, Liang Fang, Li-Gang Ma
The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating JAK2/STAT signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by TUNEL assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, Bcl2 and Bax were detected by qRT-PCR and Western blotting...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28521469/licochalcone-e-induces-caspase-dependent-death-of-human-pharyngeal-squamous-carcinoma-cells-through-the-extrinsic-and-intrinsic-apoptotic-signaling-pathways
#3
Sang-Joun Yu, In-A Cho, Kyeong-Rok Kang, Yi-Ra Jung, Seung Sik Cho, Goo Yoon, Ji-Su Oh, Jae-Seek You, Yo-Seob Seo, Gyeong-Je Lee, Sook-Young Lee, Do Kyung Kim, Chun Sung Kim, Su-Gwan Kim, Mi-Ae Jeong, Jae-Sung Kim
The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico-E exhibited significant cytotoxicity on FaDu cells in a concentration-dependent manner. The IC50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico-E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico-E for 24 h...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#4
Donatella Delle Cave, Vincenzo Desiderio, Laura Mosca, Concetta Paola Ilisso, Luigi Mele, Michele Caraglia, Giovanna Cacciapuoti, Marina Porcelli
The naturally-occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28513772/etanercept-protects-rat-cardiomyocytes-against-hypertrophy-by-regulating-inflammatory-cytokines-secretion-and-cell-apoptosis
#5
Q Li, Q Yu, R Na, B Liu
We aimed to investigate the effect of etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, on rat cardiomyocyte hypertrophy and its underlying mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and then treated with different concentrations of etanercept (1, 10, and 50 μM). After treatment, cell counts, viability and cell apoptosis were evaluated. The mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT-PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were measured by western blotting...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28512446/neuroprotective-roles-of-l-cysteine-in-attenuating-early-brain-injury-and-improving-synaptic-density-via-the-cbs-h2s-pathway-following-subarachnoid-hemorrhage-in-rats
#6
Tong Li, Lingxiao Wang, Quan Hu, Song Liu, Xuemei Bai, Yunkai Xie, Tiantian Zhang, Shishi Bo, Xiangqian Gao, Shuhua Wu, Gang Li, Zhen Wang
l-Cysteine is a semi-essential amino acid and substrate for cystathionine-β-synthase (CBS) in the central nervous system. We previously reported that NaHS, an H2S donor, significantly alleviated brain damage after subarachnoid hemorrhage (SAH) in rats. However, the potential therapeutic value of l-cysteine and the molecular mechanism supporting these beneficial effects have not been determined. This study was designed to investigate whether l-cysteine could attenuate early brain injury following SAH and improve synaptic function by releasing endogenous H2S...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28507277/notch1-regulates-the-jnk-signaling-pathway-and-increases-apoptosis-in-hepatocellular-carcinoma
#7
Chengxu Sui, Chengjun Zhuang, Deguang Sun, Li Yang, Liang Zhang, Lei Song
Notch1-induced pathways are involved in cell growth, apoptosis, motility, and invasion in many cancers. In the present study, the expression of Notch1 and NICD1 was detected in hepatocellular carcinoma (HCC) tissues using in-vitro assays. And then, we explored cell biology and signaling pathways using Notch1 siRNA or plasmids. Here, the expression of Notch1 and NICD1 was significantly decreased in HCC tissues. In-vitro, Notch1 plasmids inhibited cell proliferation, migration and invasion, but enhanced apoptosis of HepG2 and Hep3B cells...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502298/-forkhead-domain-inhibitor-6-fdi-6-increases-apoptosis-and-inhibits-invasion-and-migration-of-laryngeal-carcinoma-cells-by-down-regulating-nuclear-foxm1
#8
Yanan Liu, Lin Zhu, Taoyu Wen, Jie Wan, Yue Lei, Hongyan Chen
Objective To study the effects of new small molecular inhibitor, forkhead domain inhibitor-6 (FDI-6), on proliferation, apoptosis, invasion and migration in human laryngeal carcinoma Hep-2 cell line and the related mechanism. Methods MTT assay was used to test the proliferation rate of Hep-2 cells before and 12, 24 hours after treated with (5, 10, 20, 40, 80) μmol/L of FDI-6. Flow cytometry (FCM) and Transwell(TM) chamber assay were respectively carried out to detect the apoptosis rate, cell invasion and migration in Hep-2 cells after treated by 10, 20 μmol/L FDI-6 for 24 hours...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28500842/ppa1-regulates-tumor-malignant-potential-and-clinical-outcome-of-colon-adenocarcinoma-through-jnk-pathways
#9
Ping Wang, Yi Zhou, Qi Mei, Jing Zhao, Liu Huang, Qiang Fu
Colorectal cancer (CRC) represents one of the most prevalent malignancies and the third leading cause of cancer death worldwide. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate, therefore participates in the energy metabolism. Proteomic studies have demonstrated the up-regulated expression of PPA1 in various tumors, however, its expression pattern in CRC hasn't been reported. In the current study, we used RT-qCR, Western Blot and immunohistochemical (IHC) staining to explore the expression of PPA1 in 113 paired colon cancer tissues and adjacent normal tissues, which revealed that PPA1 was correlated with lymph node metastasis...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28500761/melatonin-ameliorates-myocardial-ischemia-reperfusion-injury-through-sirt3-dependent-regulation-of-oxidative-stress-and-apoptosis
#10
Mengen Zhai, Buying Li, Weixun Duan, Lin Jing, Bin Zhang, Meng Zhang, Liming Yu, Zhenhua Liu, Bo Yu, Kai Ren, Erhe Gao, Yang Yang, Hongliang Liang, Zhenxiao Jin, Shiqiang Yu
Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the sirtuin family that is localized primarily to the mitochondria and protects against oxidative stress-related diseases, including myocardial ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R injury by activating the SIRT3 signaling pathway. In this study, mice were pre-treated with or without a selective SIRT3 inhibitor and then subjected to MI/R operation...
May 13, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28498459/inhibitors-of-parp-1-exert-inhibitory-effects-on-the-biological-characteristics-of-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#11
Xiaorong Mao, Senrong Du, Zhongxia Yang, Liting Zhang, Xuebin Peng, Ni Jiang, Haiyu Zhou
It has been confirmed that the inhibitors of poly ADP-ribose polymerF(^9ase‑1 (PARP‑1) can inhibit the proliferation, apoptosis and invasion of tumor cells. However, the effects of inhibitors of PARP‑1 on hepatocellular carcinoma remain to be elucidated. The aim of the present study was to investigate the effect of three types of PARP‑1 inhibitor on the proliferation, apoptosis and migration of hepatocellular carcinoma in vitro. An MTT assay was performed to detect the proliferation of HepG2 cells following treatment with the PARP‑1 inhibitors, AG014699, BSI‑201 and AZD‑2281...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28495516/7-o-geranylquercetin-induced-autophagy-contributes-to-apoptosis-via-ros-generation-in-human-non-small-cell-lung-cancer-cells
#12
En-Xia Wang, Bo-Yang Zou, Lei Shi, Lin-Ying Du, Yan-Yan Zhu, Ya-Meng Jiang, Xiao-Dong Ma, Xiao-Hui Kang, Chang-Yuan Wang, Yu-Hong Zhen, Li-Dan Sun
AIMS: To investigate the antitumor effects of 7-O-geranylquercetin (GQ), a novel O-alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. MAIN METHODS: Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay...
May 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28492339/venetoclax-for-the-treatment-of-patients-with-chronic-lymphocytic-leukemia
#13
Jennifer Crombie, Matthew S Davids
Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp-up and close tumor lysis syndrome monitoring and prophylaxis...
May 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28491103/oleuropein-protects-cardiomyocyte-against-apoptosis-via-activating-the-reperfusion-injury-salvage-kinase-pathway-in-vitro
#14
Qiming Zhao, Yinliang Bai, Caie Li, Kun Yang, Wansheng Wei, Zhenzhen Li, Li Pan, Xiaoming Li, Xuanfen Zhang
Oleuropein, the main glycoside present in olives, has been reported to have cardioprotective effect, but the exact mechanism has not been clearly elucidated. This study attempted to clarify the cardioprotective effect of oleuropein against simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and further explore the underlying mechanism. Here we confirmed that oleuropein reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced by decreasing MTT dye reduction and LDH activity in the culture medium...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28490320/astaxanthin-protects-astrocytes-against-trauma-induced-apoptosis-through-inhibition-of-nkcc1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Mingkun Zhang, Zhenwen Cui, Hua Cui, Yong Wang, Chunlong Zhong
BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic pharmacological properties that is seen as a possible drug for treating cerebral ischemic injury and subarachnoid hemorrhage. Na(+)-K(+)-2Cl(-) co-transporter-1 (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated by various insults, leading to the formation of cell swelling and brain edema. We previously established that ATX attenuated brain edema and improved neurological outcomes by modulating NKCC1 expression after traumatic brain injury in mice...
May 10, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28488455/intracellular-methylglyoxal-induces-oxidative-damage-to-pancreatic-beta-cell-line-ins-1-cell-through-ire1%C3%AE-jnk-and-mitochondrial-apoptotic-pathway
#16
Chongxiao Liu, Yanhong Huang, Yifan Zhang, Xueru Chen, Xiang Kong, Yan Dong
An increased intracellular methylglyoxal (MGO) under hyperglycemia led to pancreatic beta cell death. However, its mechanism in which way with MGO induced beta cell death remains unknown. We investigated both high glucose and MGO treatment significantly inclined intracellular MGO concentration and inhibited cell viability in vitro. MGO treatment also triggered intracellular advanced glycation end products (AGEs) formation, declined mitochondrial membrane potential (MMP), increased oxidative stress and the expression of ER stress mediators Grp78/Bip and p-PERK; activated mitochondrial apoptotic pathway, which could mimic by Glo1 knockdown...
May 10, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28487980/combination-of-bortezomib-and-daunorubicin-in-the-induction-of-apoptosis-in-t-cell-acute-lymphoblastic-leukemia
#17
Xin Du, Jia Tong, Hongying Lu, Cong He, Shenghong Du, Peimin Jia, Weili Zhao, Hanzhang Xu, Junmin Li, Zhixiang Shen, Yingli Wu, Jianhua Tong, Li Zhou
Despite advances in the treatment of T‑cell acute lymphoblastic leukemia (T‑ALL), the outcome of T‑ALL treatment remains unsatisfactory, therefore, more effective treatment is urgently required. The present study examined the cytotoxicities of bortezomib in combination with daunorubicin against human Jurkat and Molt‑4 T‑ALL cells and primary T‑ALL cells. Compared with treatment alone, co‑exposure of cells to bortezomib and daunorubicin resulted in a significant increase in cell death in the Jurkat cells, as evidenced by the increased percentage of Annexin V‑positive cells, the formation of apoptotic bodies...
May 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487945/nox4-is-involved-in-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells-via-notch-pathway
#18
Min Yao, Feng Gao, Xiaomeng Wang, Yonghong Shi, Shuxia Liu, Huijun Duan
It has previously been demonstrated that nicotinamide adenine dinucleotide phosphate‑oxidase (NADPH) oxidase 4 (Nox4), is important in the pathogenesis of diabetic nephropathy (DN), however the exact mechanisms remain to be elucidated. The present study aimed to examine the effect of Nox4 on the alteration of the Notch pathway and cell apoptosis in the renal tubular epithelial cell line, HKC, under conditions of high glucose (HG; 30 mmol/l glucose). Nox4 and the Notch pathway were inhibited by N‑acetylcysteine (NAC), diphenylene iodonium (DPI) or γ‑secretase inhibitor (DAPT)...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487599/mir-195-regulates-proliferation-and-apoptosis-through-inhibiting-the-mtor-p70s6k-signaling-pathway-by-targeting-hmga2-in-esophageal-carcinoma-cells
#19
Yong Li, Dapeng Wu, Pei Wang, Xiaohui Li, Gongning Shi
miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated...
2017: Disease Markers
https://www.readbyqxmd.com/read/28486965/site-specific-gene-expression-patterns-in-oral-cancer
#20
Gesche Frohwitter, Horst Buerger, Eberhard Korsching, Paul J van Diest, Johannes Kleinheinz, Thomas Fillies
BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity...
May 10, 2017: Head & Face Medicine
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