Read by QxMD icon Read

Bcl-2 family proteins

Stefan M Ivanov, Roland G Huber, Jim Warwicker, Peter J Bond
Critical regulatory pathways are replete with instances of intra- and interfamily protein-protein interactions due to the pervasiveness of gene duplication throughout evolution. Discerning the specificity determinants within these systems has proven a challenging task. Here, we present an energetic analysis of the specificity determinants within the Bcl-2 family of proteins (key regulators of the intrinsic apoptotic pathway) via a total of ∼20 μs of simulation of 60 distinct protein-protein complexes. We demonstrate where affinity and specificity of protein-protein interactions arise across the family, and corroborate our conclusions with extensive experimental evidence...
October 17, 2016: Structure
Fan-Shiu Tsai, Li-Wei Lin, Chi-Rei Wu
Lupeol belongs to pentacyclic lupane-type triterpenes and exhibits in edible vegetables, fruits and many plants. Many researches indicated that lupeol possesses many beneficial pharmacological activities including antioxidant, anti-inflammatory, anti-hyperglycemic, anti-dyslipidemic and anti-mutagenic effects. From various disease-targeted animal models, these reports indicated that lupeol has anti-diabetic, anti-asthma, anti-arthritic, cardioprotective, hepatoprotective, nephroprotective, neuroprotective and anticancer efficiency under various routes of administration such as topical, oral, subcutaneous, intraperitoneal and intravenous...
2016: Advances in Experimental Medicine and Biology
Feixiong Cheng, Junfei Zhao, Ariella B Hanker, Monica Red Brewer, Carlos L Arteaga, Zhongming Zhao
PURPOSE: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer. Furthermore, PIK3CA mutations are commonly associated with resistance to anti-epidermal growth factor receptor 2 (HER2) or anti-estrogen receptor (ER) agents in HER2 or ER positive (HER2(+)/ER(+)) breast cancer. Hence, deciphering the underlying mechanisms of PIK3CA mutations in HER2(+)/ER(+) breast cancer would provide novel insights into elucidating resistance to anti-HER2/ER therapies...
October 22, 2016: Breast Cancer Research and Treatment
Yun Bai, Jia Wang, Jing Han, Xiao-Li Xie, Cheng-Guang Ji, Jie Yin, Lei Chen, Cun-Kai Wang, Xiao-Yu Jiang, Wei Qi, Hui-Qing Jiang
BACKGROUND AND AIMS: BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. METHODS: BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice...
October 22, 2016: Molecular Carcinogenesis
Yi-Xin Wu, Jia-Hua Yang, Hirotomo Saitsu
Bortezomib (BTZ), a proteasome inhibitor, is the first proteasome inhibitor to be used in clinical practice. Here we investigated the mechanisms underlying acquired bortezomib resistance in hepatocellular carcinoma (HCC) cells. Using stepwise selection, we established two acquired bortezomib-resistant HCC cell lines, a bortezomib-resistant HepG2 cell line (HepG2/BTZ) and bortezomib-resistant HuH7 cell line (HuH7/BTZ). The 50% inhibitory concentration values of HepG2/BTZ and HuH7/BTZ were respectively 15- and 39-fold higher than those of parental cell lines...
October 18, 2016: Oncotarget
Robert F Gahl, Pallavi Dwivedi, Nico Tjandra
The most critical step in the initiation of apoptosis is the activation of the Bcl-2 family of proteins to oligomerize and permeabilize the outer-mitochondrial membrane (OMM). As this step results in the irreversible release of factors that enhance cellular degradation, it is the point of no return in programmed cell death and would be an ideal therapeutic target. However, the arrangement of the Bcl-2 proteins in the OMM during permeabilization still remains unknown. It is also unclear whether the Bcl-2 protein, Bid, directly participates in the formation of the oligomers in live cells, even though it is cleaved and translocates to the OMM at the initiation of apoptosis...
October 20, 2016: Cell Death & Disease
Vicente Andreu-Fernandez, Maria J García-Murria, Manuel Bañó-Polo, Juliette Martin, Luca Monticelli, Mar Orzáez, Ismael Mingarro
Changes in the equilibrium of pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family in the mitochondrial outer membrane (MOM) induce structural changes that commit cells to apoptosis. Bcl-2 homology-3 (BH3)-only proteins participate in this process by either activating pro-apoptotic effectors or inhibiting anti-apoptotic components and by promoting MOM permeabilization. The association of BH3-only proteins with MOMs is necessary for the activation and amplification of death signals; however, the nature of this association remains controversial, as these proteins lack a canonical transmembrane sequence...
October 7, 2016: Journal of Biological Chemistry
Narayan Dolai, Aminul Islam, Pallab Kanti Haldar
OBJECTIVE: Anthocephalus cadamba (Roxb.) Miq. (Family: Rubiaceae), a folk medicine commonly known as "Kadam" in Bengali, has been used for the treatment of tumor. The methanolic extract of A. cadamba (MEAC) showing antitumor activity on Ehrlich ascites carcinoma (EAC) cells treated mice was already reported. This study was designed to study the apoptosis-inducing property of MEAC and its mechanism in EAC cells in mice. MATERIALS AND METHODS: Apoptogenic morphology was determined by fluorescent DNA-binding double staining method using dyes acridine orange (AO)/ethidium bromide (EB)...
July 2016: Indian Journal of Pharmacology
Li Zhang, Si-Yuan Kong, Zhao-Qing Zheng, Xiao-Xiao Meng, Ji-Ling Feng, Hong-Sheng Tan, Yuan-Zhi Lao, Lian-Bo Xiao, Hong-Xi Xu
Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation...
October 12, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Wenwen Wang, Yanqin Yang, Zhewen Xiong, Jiamin Kong, Xinlu Fu, Feihai Shen, Zhiying Huang
Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes...
October 14, 2016: Toxicology and Applied Pharmacology
Jeremy L Yap, Lijia Chen, Maryanna E Lanning, Steven Fletcher
A hallmark of cancer is the evasion of apoptosis, which is often associated with the upregulation of the anti-apoptotic members of the Bcl-2 family of proteins. The prosurvival function of the anti-apoptotic Bcl-2 proteins is manifested by capturing the pro-apoptotic Bcl-2 proteins through their BH3 death domains. Accordingly, strategies to antagonize the anti-apoptotic Bcl-2 proteins have largely focused on the development of low-molecular-weight, synthetic and selective BH3 mimetics ("magic bullets") to disrupt the protein-protein interactions between anti- and pro-apoptotic Bcl-2 proteins...
October 17, 2016: Journal of Medicinal Chemistry
Xiubing Zhang, Lu Hua, Daliang Yan, Fengbo Zhao, Jinxia Liu, Huiling Zhou, Jie Liu, Miaomiao Wu, Chengliang Zhang, Yingying Chen, Buyou Chen, Baoying Hu
Poly(C)‑binding protein 2 (PCBP2) is a member of the PCBP family, and plays an important role in post‑transcriptional and translational regulation of various signaling molecules through direct binding to single‑stranded poly(C) motifs. PCBP2 has been reported to play a critical role in the development of multiple human tumors. However, whether PCBP2 participates in hepatocellular carcinoma (HCC) development remains largely elusive. Herein, we showed that PCBP2 was upregulated in human HCC tissues and cell lines...
October 13, 2016: Oncology Reports
Lijia Chen, Steven Fletcher
The myeloid cell leukemia -1 (MCL-1) protein is one of the key anti-apoptotic protein members of the B-cell lymphoma-2 (BCL-2) protein family. Over-expression of MCL-1 has been closely related to tumor progression as well as resistance to not only traditional chemotherapies but also targeted therapeutics including BCL-2 inhibitors such as ABT-263. Therefore, extensive research and development in the last fifteen years in both academic and industrial settings to address this unmet medical need. Areas covered: This review covers research and patent literature of the past 10 years in the field of discovery and development of small-molecule inhibitors of the MCL-1 anti-apoptotic protein...
October 17, 2016: Expert Opinion on Therapeutic Patents
Fabio Arturo Grieco, Guido Sebastiani, Jonas Juan-Mateu, Olatz Villate, Laura Marroqui, Laurence Ladrière, Ksenya Tugay, Romano Regazzi, Marco Bugliani, Piero Marchetti, Francesco Dotta, Décio L Eizirik
Type 1 Diabetes is an autoimmune disease leading to beta cell destruction. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to beta cell death in T1D and their target genes remain to be clarified.We performed a miRNA expression profile on human islet preparations exposed to the cytokines IL-1β+IFN-γ. Confirmation of miRNAs and target genes modification in human beta cells was performed by real-time qPCR...
October 13, 2016: Diabetes
Jonathan Schwartz, Xiaojia Niu, Eric Walton, Laura Hurley, Hai Lin, Holly Edwards, Jeffrey W Taub, Zhihong Wang, Yubin Ge
Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus new treatment strategies are needed for this deadly disease. Poor clinical outcomes have been associated with overexpression of the anti-apoptotic Bcl-2 family proteins Bcl-2, Bcl-xL, and Mcl-1, which have garnered great interest as therapeutic targets. While the Bcl-2-selective inhibitor ABT-199 has demonstrated promising preclinical anti-leukemic activities, intrinsic drug resistance remains a problem. In our most recent study, we identified Mcl-1 sequestration of Bim as a mechanism of intrinsic resistance to ABT-199 in AML cells, thus upregulating Bim could overcome such resistance...
2016: American Journal of Translational Research
K Matsuura, N-J Huang, K Cocce, L Zhang, S Kornbluth
Evasion of apoptosis allows many cancers to resist chemotherapy. Apoptosis is mediated by the serial activation of caspase family proteins. These proteases are often activated upon the release of cytochrome c from the mitochondria, which is promoted by the proapoptotic Bcl-2 family protein, Bax. This function of Bax is enhanced by the MOAP-1 (modulator of apoptosis protein 1) protein in response to DNA damage. Previously, we reported that MOAP-1 is targeted for ubiquitylation and degradation by the APC/C(Cdh1) ubiquitin ligase...
October 10, 2016: Oncogene
Xiaoxing Huang, Wei Huang, Li Li, Xihuan Sun, Siyang Song, Qingyan Xu, Lianru Zhang, Bang-Guo Wei, Xianming Deng
Marine natural products are served as attractive source of anticancer therapeutics, with the great success of "first-in-class" drugs, such as Yondelis, Halaven, and Brentuximab vendotin. Lagunamides A-C from marine cyanobacterium, Lyngbya majuscula, exhibit exquisite growth inhibitory activities against cancer cells. In this study, we have systematically investigated the structure-activity relationships (SAR) of a concise collection of lagunamide A and its analogs constructed by total chemical synthesis against a broad panel of cancer cells derived from various tissues or organs, including A549, HeLa, U2OS, HepG2, BEL-7404, BGC-823, HCT116, MCR-7, HL-60, and A375...
October 7, 2016: Molecular Pharmaceutics
Qiu-Lin Ge, San-Hong Liu, Zhi-Hong Ai, Min-Fang Tao, Li Ma, Shan-Yun Wen, Miao Dai, Fei Liu, Han-Shao Liu, Rong-Zhen Jiang, Zhuo-Wei Xue, Yu-Hang Jiang, Xiao-Hua Sun, Yi-Ming Hu, Yong-Xu Zhao, Xi Chen, Yu Tao, Xiao-Lu Zhu, Wen-Jing Ding, Bing-Qing Yang, Dan-Dan Liu, Xiao-Ren Zhang, Yin-Cheng Teng
Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC)...
October 6, 2016: Cell Death & Disease
J Zhang, J H Liang, J G Huang
Osteosarcoma (OS) causes millions of death worldwide and, since there is no effective therapy, it is necessary to identify the molecular mechanism of OS, which can direct the development of new therapies. This study investigated the role of bone morphogenetic protein 9 (BMP9), a member of the transforming growth factor (TGF)-β family, in OS development. This study first examined BMP9 expression in tissue from OS patients and normal subjects. The OS cell line (MG63) and tumor cells from OS patients were then transfected with BMP9 and cell proliferation and apoptosis were assessed...
September 16, 2016: Genetics and Molecular Research: GMR
Jung Min Kim, In-Hu Hwang, Ik-Soon Jang, Min Kim, In Seok Bang, Soo Jung Park, Yun-Jo Chung, Jong-Cheon Joo, Min-Goo Lee
Houttuynia cordata Thunb (H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells...
October 3, 2016: Integrative Cancer Therapies
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"