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Bcl-2 protein inhibitors

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https://www.readbyqxmd.com/read/28531921/hesperetin-post-treatment-prevents-rat-cardiomyocytes-from-hypoxia-reoxygenation-injury-in-vitro-via-activating-pi3k-akt-signaling-pathway
#1
Shangfei He, Xianbao Wang, Yongkang Zhong, Lu Tang, Ya Zhang, Yuanna Ling, Zhipeng Tan, Pingzhen Yang, Aihua Chen
Hesperidin (HES), a citrus fruit extract, has beneficial effects on various ischemia/reperfusion (I/R) models. Here, we investigated the possible positive effect of hesperetin (HPT), an active metabolite of HES, and identified the potential molecular mechanisms involved in cardiomyocytes H/R-induced injury. To construct the cardiomyocyte model of hypoxia/reoxygenation (H/R) injury, cultured neonatal rat cardiomyocytes were subjected to 3h of hypoxia followed by 3h of reoxygenation. Cell viability and apoptosis were detected...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531803/isofraxidin-inhibited-proliferation-and-induced-apoptosis-via-blockage-of-akt-pathway-in-human-colorectal-cancer-cells
#2
Peng Shen, Hong-Gang Wang, Miao-Miao Li, Qian-Yun Ma, Chuan-Wen Zhou, Feng Pan, Rui Xie
BACKGROUND: Isofraxidin (IF), a natural coumarin compound, has been reported to possess anti-cancer activity in human liver cancer. However, whether IF is involved in the regulation of colorectal cancer tumorigenesis and development has been not well elucidated. METHODS: The cell proliferation were assessed by Cell Counting Kit-8 (CCK-8) and colony formation test, respectively. The transwell assays were conducted to estimate cell migration and invasion abilities...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28529715/inducing-death-in-tumor-cells-roles-of-the-inhibitor-of-apoptosis-proteins
#3
REVIEW
Darren Finlay, Peter Teriete, Mitchell Vamos, Nicholas D P Cosford, Kristiina Vuori
The heterogeneous group of diseases collectively termed cancer results not just from aberrant cellular proliferation but also from a lack of accompanying homeostatic cell death. Indeed, cancer cells regularly acquire resistance to programmed cell death, or apoptosis, which not only supports cancer progression but also leads to resistance to therapeutic agents. Thus, various approaches have been undertaken in order to induce apoptosis in tumor cells for therapeutic purposes. Here, we will focus our discussion on agents that directly affect the apoptotic machinery itself rather than on drugs that induce apoptosis in tumor cells indirectly, such as by DNA damage or kinase dependency inhibition...
2017: F1000Research
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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/28502298/-forkhead-domain-inhibitor-6-fdi-6-increases-apoptosis-and-inhibits-invasion-and-migration-of-laryngeal-carcinoma-cells-by-down-regulating-nuclear-foxm1
#10
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
#11
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/28498459/inhibitors-of-parp-1-exert-inhibitory-effects-on-the-biological-characteristics-of-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#12
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
#13
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/28490320/astaxanthin-protects-astrocytes-against-trauma-induced-apoptosis-through-inhibition-of-nkcc1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway
#14
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/28487980/combination-of-bortezomib-and-daunorubicin-in-the-induction-of-apoptosis-in-t-cell-acute-lymphoblastic-leukemia
#15
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
#16
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/28486965/site-specific-gene-expression-patterns-in-oral-cancer
#17
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
https://www.readbyqxmd.com/read/28486954/mir-486-regulates-cardiomyocyte-apoptosis-by-p53-mediated-bcl-2-associated-mitochondrial-apoptotic-pathway
#18
Yuhan Sun, Qiang Su, Lang Li, Xiantao Wang, Yuanxi Lu, Jiabao Liang
BACKGROUND: Cardiomyocyte apoptosis is a common pathological manifestation that occurs in several heart diseases. This study aimed to explore the mechanism of microRNA-486 (miR-486) in cardiomyocyte apoptosis by interfering with the p53-activated BCL-2 associated mitochondrial pathway. METHODS: miR-486 mimics and inhibitors were transfected into the primary cardiomyocytes of suckling Sprague-Dawley rat pups, and H2O2 was used to induce apoptosis. Flow cytometry and TUNEL were both used to detect cardiomyocyte apoptosis, while the relative mRNA transcript and protein levels of miR-486, p53, Bbc3, BCL-2, and cleaved caspase-3 were detected using RT-PCR and western blot analysis, respectively...
May 10, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28482721/the-potential-combination-of-bcl-2-inhibitors-and-ibrutinib-as-frontline-therapy-in-chronic-lymphocytic-leukemia
#19
Andrew Aw, Jennifer R Brown
The recent development of small molecule inhibitors targeted at the B-cell receptor (BCR) pathway and the anti-apoptotic protein BCL-2 has revolutionized the care of patients with chronic lymphocytic leukemia (CLL). While durable responses to the BCR inhibitor ibrutinib have been observed in both previously untreated and relapsed/refractory CLL patients, residual disease is common in patients treated with single-agent ibrutinib. Interest remains high in therapeutic combinations that may lead to better quality remissions...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28478808/anticancer-activities-of-harmine-by-inducing-a-pro-death-autophagy-and-apoptosis-in-human-gastric-cancer-cells
#20
Chuan Li, Yihai Wang, Chunhua Wang, Xiaomin Yi, Mingya Li, Xiangjiu He
BACKGROUND: Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear. PURPOSE: To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells. METHODS/STUDY DESIGNS: The anti-proliferative activity of harmine in vitro was evaluated by MTT assay...
May 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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