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Céline Vuillier, Steven Lohard, Aurélie Fétiveau, Jennifer Allègre, Cémile Kayaci, Louise E King, Frédérique Braun, Sophie Barillé-Nion, Fabien Gautier, Laurence Dubrez, Andrew P Gilmore, Philippe P Juin, Laurent Maillet
E2F1 is the main pro-apoptotic effector of the pRB-regulated tumor suppressor pathway by promoting the transcription of various pro-apoptotic proteins. We report here that E2F1 partly localizes to mitochondria, where it favors mitochondrial outer membrane permeabilization. E2F1 interacts with BCL-xL independently from its BH3 binding interface and induces a stabilization of BCL-xL at mitochondrial membranes. This prevents efficient control of BCL-xL over its binding partners, in particular over BAK resulting in the induction of cell death...
December 12, 2017: EMBO Reports
Xiaohua Liu, Yu Zhang, Wenjing Huang, Wenfu Tan, Ao Zhang
The antiapoptotic protein Bcl-2, overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, we report a different structural modification approach on ABT-263 by merging the piperazinyl-phenyl fragment into a bicyclic framework leading to a series of novel analogues, among which tetrahydroisoquinoline 13 was nearly equally potent against Bcl-2 as ABT-263. Further SAR in the P4-interaction pocket affored the difluoroazetidine substituted analogue 55, which retained good Bcl-2 activity with improved Bcl-2/Bcl-xL selectivity...
December 5, 2017: Bioorganic & Medicinal Chemistry
Ji-Hyun Park, Young Ho Seo, Jung-Hee Jang, Chul-Ho Jeong, Sooyeun Lee, Byoungduck Park
BACKGROUND: Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway...
December 11, 2017: Journal of Neuroinflammation
Ligang Ma, Jingjing Zhao, Xiaojuan Xie
This study aimed to detect the effect of sevoflurane anesthesia on liver injury through modulating IGF-1. The expression of IGF-1 and IGF-1R in liver tissues of sevoflurane-exposed rats was examined by qRT-PCR and western blot. The expression levels of miR-214 in liver cells treated with different concentration of sevoflurane at different time points were detected by qRT-PCR. Enzyme-linked immunosorbent (ELISA) assay was used to analyze serum IGF-1 concentration in cell culture media. After pre-treatment with 100 nM miR-214 inhibitor followed by exposure to sevoflurane, the expression level of miR-214 and IGF-1 protein in liver cells was examined...
December 11, 2017: Journal of Cellular Physiology
Chao-Yan Wu, Yuan Ke, Yi-Fei Zeng, Ying-Wen Zhang, Hai-Jun Yu
Background: We have reported that Chinese herbs Astragalus polysaccharide (APS) can inhibit nuclear factor kappaB (NF-κB) activity during the development of diabetic nephropathy in mice. NF-κB plays important roles in genesis, growth, development and metastasis of cancer. NF-κB is also involved in the development of treatment resistance in tumors. Here we investigated the antitumor activity of APS in human non-small cell lung cells (A549 and NCI-H358) and the related mechanisms of action...
2017: Cancer Cell International
Piyawadee Wicha, Jiraporn Tocharus, Adchara Janyou, Jinatta Jittiwat, Chatchawan Changtam, Apichart Suksamrarn, Chainarong Tocharus
The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups...
2017: PloS One
Wei-Bin Zheng, Yang-Jia Li, Yang Wang, Jie Yang, Can-Can Zheng, Xiao-Hui Huang, Bin Li, Qing-Yu He
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival and limited therapeutic options. The aim of this study is to identify novel anticancer strategies from existing Food and Drug Administration (FDA)-approved drugs that have been used to clinically treat other diseases. Here, propafenone, an antiarrhythmic medication, was found to induce apoptosis and exert a significantly inhibitory effect on the proliferation and colony-forming ability of ESCC cells in a dose-dependent manner without observed cytotoxicity on normal esophageal epithelial cells...
2017: American Journal of Cancer Research
Min Du, Gang Wen, Juan Jin, Yuanguang Chen, Jun Cao, Aman Xu
The aim of the present study was to investigate the effects of mangiferin on gastric carcinoma cells and to determine the possible mechanisms underlying such effects. The MTT assay was performed to evaluate the antiproliferative effect of mangiferin. Following treatment, apoptosis rates of SGC-7901 were established by flow cytometry and laser confocal microscopy, and western blot analysis was used to detect the expression of apoptosis-related proteins. The MTT assay showed that mangiferin inhibited the proliferation of SGC-7901 and BCG-823 cells in a dose-dependent and time-dependent manner...
December 5, 2017: Anti-cancer Drugs
Kevin M Rice, Nandini D P K Manne, Ravikumar Arvapalli, Gautam K Ginjupalli, Eric R Blough
The effect of diabetes on vascular mechano-transductive response is of great concern. Given the higher rate of vein graft failures associated with diabetes, understanding the multiple cellular and molecular events associated with vascular remodeling is of vital importance. This article represents data related to a study published in Cardiovascular Diabetology [1] (Rice et al., 2006) and Open Journal of Endocrine and Metabolic Diseases [2] (Rice et al., 2015) evaluating the effect of pressurization on rat inferior venae cavae (IVC)...
December 2017: Data in Brief
Liang Chen, Ya-Qiong Xiong, Jing Xu, Ji-Peng Wang, Zi-Li Meng, Yong-Qing Hong
Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare, exerting suppressive activity against cancer cell progression in vitro and in vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation...
November 7, 2017: Oncotarget
Jihong Shi, Shan Shi, Bin Wu, Jian Zhang, Yan Li, Xue Wu, Julei Zhang, Kejia Wang, Bin Zhao, Weixia Cai, Xiaozhi Bai, Dahai Hu, Hao Guan
Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by excessive hypercellularity and extracellular matrix (ECM) component deposition. Autophagy is a tightly regulated physiological process essential for cellular maintenance, differentiation, development and homeostasis. However, during the formation of HS, whether and how autophagy is regulated in dermal fibroblasts are still far from elucidated. Here we detected the autophagic capacity in HS and normal skin (NS) counterparts, explored and verified the key regulatory molecules of autophagy in HS-derived fibroblasts (HSFs), and validated the data using rabbit ear scar model...
November 7, 2017: Oncotarget
Liyan Jiang, Di Wang, Yongfeng Zhang, Junyang Li, Zhiping Wu, Zhi Wang, Di Wang
Arbutin, a natural polyphenol isolated from the bearberry plant Arctostaphylos uvaursi, possesses whitening and anticancer properties. The effects of arbutin on melanogenesis and its pro-apoptotic effect on B16 murine melanoma cells have not yet been reported. In the present study, acetylated arbutin was prepared in order to improve the biological effects of arbutin, and it was found to significantly inhibit the biosynthesis of melanin and tyrosinase activity compared with parent arbutin in B16 murine melanoma cells...
November 16, 2017: International Journal of Molecular Medicine
Meng Liu, Zheng Han, Qing-Xi Zhu, Jie Tan, Wei-Jie Liu, Yan-Fen Wang, Wei Chen, Yan-Li Zou, Yi-Shan Cai, Xia Tian, Xiaodong Huang
Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the mechanism of enhancing cisplatin-inducing effects on human gastric cancer BGC823 cells by blocking CDH17 gene, both in vitro and in vivo, remains to be clarified. In this study, we investigated the signaling pathway by which cisplatin induces apoptosis by blocking CDH17 gene in gastric cancer BGC823 cells...
December 4, 2017: Cancer Gene Therapy
Dae Woo Choi, Do Kyung Kim, Yoshikatsu Kanai, Michael F Wempe, Hitoshi Endou, Jong-Keun Kim
Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak...
November 2017: Korean Journal of Physiology & Pharmacology
Tao Jiang, Xiu-Qin Wang, Chuan Ding, Xue-Lian Du
Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats...
November 2017: Korean Journal of Physiology & Pharmacology
Zachary B Hill, Alexander J Martinko, Duy P Nguyen, James A Wells
Chemically induced dimerizers (CIDs) have emerged as one of the most powerful tools for artificially regulating signaling pathways in cells; however, currently available CID systems lack the properties desired for use in regulating cellular therapies. Here, we report the development of human antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule-protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. We demonstrate this concept by generating three antibodies that are highly selective for the BCL-xL-ABT-737 complex compared to BCL-xL alone...
December 4, 2017: Nature Chemical Biology
Naoki Wakui, Ryunosuke Yoshino, Nobuaki Yasuo, Masahito Ohue, Masakazu Sekijima
B-cell lymphoma 2 (Bcl-2) family proteins are potential drug targets in cancer and have a relatively flat and flexible binding site. ABT-199 is one of the most promising selective Bcl-2 inhibitors, and A-1155463 selectively inhibits Bcl-XL. Although the amino acid sequences of the binding sites of these two inhibitors are similar, the inhibitors selectively bind the target protein. In order to determine the origin of the selectivity of these inhibitors, we conducted molecular dynamics simulations using protein-inhibitor modeling...
November 23, 2017: Journal of Molecular Graphics & Modelling
Andy Wei-Ge Chen, Yen-Shuo Tseng, Chia-Chieh Lin, Yi-Ting Hsi, Yu-Sheng Lo, Yi-Ching Chuang, Shu-Hui Lin, Chia-Yun Yu, Ming-Ju Hsieh, Mu-Kuan Chen
While Nasopharyngeal carcinoma (NPC) is uncommon in western countries, it is endemic in Southeast Asia and Southern China. Previous study of norcantharidin (NCTD), isolated from blister beetles, has proved its anticancer effect on various tumors. However, the effect of NCTD in NPC has never been studied. The purpose of this study is to inspect the suppression activity of NCTD on NPC, along with the underlying mechanism. NPC cell line NPC-BM was treated with NCTD. NCTD remarkably inhibited proliferation and induce apoptosis in NPC-BM cell...
November 29, 2017: Environmental Toxicology
Xiaoyin Xu, Hiroaki Iwasa, Shakhawoat Hossain, Aradhan Sarkar, Junichi Maruyama, Kyoko Arimoto-Matsuzaki, Yutaka Hata
RASSF6, a member of the tumor suppressor Ras-association domain family proteins, induces apoptosis in the caspase-dependent and caspase-independent manners. RASSF6 interacts with MDM2 and stabilizes p53. BCL-XL is a prosurvival member of BCL-2 family proteins. BCL-XL directly inhibits proapoptotic BAX and BAK. BCL-XL also traps tBID, a proapoptotic activator BH3-only protein, and sequesters p53. In addition, BCL-XL regulates the mitochondrial membrane permeability via voltage-dependent anion channel. In these manners, BCL-XL plays an antiapoptotic role...
November 28, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Farui Sun, Yuanjin Zhang, Lijun Xu, Songbai Li, Xiang Chen, Ling Zhang, Yifan Wu, Jun Li
Although cisplatin has been proved as an integral part of chemotherapy regiment in osteosarcoma (OS) treatment, toxicity issues and chemoresistance hindered the OS therapeutic development. Exploring novel combination therapy methods is required to circumvent the limitations of cisplatin alone. The proteasome inhibitor MG132 has shown its anti-tumor effects in many solid tumors. However, little is known about its effects in combination with cisplatin in osteosarcoma cells. In this study, we examined the effects of MG132 in combination with cisplatin in human osteosarcoma cells (MG-63 and HOS)...
November 30, 2017: Oncology Research
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