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Bcl-2 family proteins

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https://www.readbyqxmd.com/read/28630157/pore-formation-by-dimeric-bak-and-bax-an-unusual-pore
#1
REVIEW
Rachel T Uren, Sweta Iyer, Ruth M Kluck
Apoptotic cell death via the mitochondrial pathway occurs in all vertebrate cells and requires the formation of pores in the mitochondrial outer membrane. Two Bcl-2 protein family members, Bak and Bax, form these pores during apoptosis, and how they do so has been investigated for the last two decades. Many of the conformation changes that occur during their transition to pore-forming proteins have now been delineated. Notably, biochemical, biophysical and structural studies indicate that symmetric homodimers are the basic unit of pore formation...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28627691/scutellaria%C3%A2-baicalensis-georgi-induces-caspase-dependent-apoptosis-via-mitogen-activated-protein-kinase-activation-and-the-generation-of-reactive-oxygen-species-signaling-pathways-in-mcf-7-breast-cancer-cells
#2
Jin Ryeong Park, Min Cheol Lee, Seong-Cheol Moon, Junghoon Kim, Ki-Tae Ha, Eun Jung Park, Chansik Hong, Byoung-Do Seo, Byung Joo Kim
Scutellaria baicalensis Georgi extract (SBGE) is used in traditional herbal medicine and has also been used clinically to ameliorate the symptoms of various inflammatory diseases and cancer. In women, breast cancer is one of the most common diseases and numerous women succumb to it. The present study was undertaken to investigate the mechanism responsible for the SBGE‑induced apoptosis of MCF‑7 human breast cancer cells. SBGE was administered to cells at concentrations between 100 and 500 mg/ml, and cell viabilities were identified using an MTT assay...
June 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627620/protective-effect-of-human-serum-amyloid-p-on-ccl4-induced-acute-liver-injury-in-mice
#3
Min Cong, Weihua Zhao, Tianhui Liu, Ping Wang, Xu Fan, Qingling Zhai, Xiaoli Bao, Dong Zhang, Hong You, Tatiana Kisseleva, David A Brenner, Jidong Jia, Hui Zhuang
Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28622296/bcl-2-family-integrating-stress-responses-at-the-er-to-control-cell-demise
#4
REVIEW
Philippe Pihán, Amado Carreras-Sureda, Claudio Hetz
In the last decade, the endoplasmic reticulum (ER) has emerged as a central organelle regulating the core mitochondrial apoptosis pathway. At the ER membrane, a variety of stress signals are integrated toward determining cell fate, involving a complex cross talk between key homeostatic pathways including the unfolded protein response, autophagy, calcium signaling and mitochondrial bioenergetics. In this context, key regulators of cell death of the BCL-2 and TMBIM/BI-1 family of proteins have relevant functions as stress rheostats mediated by the formation of distinct protein complexes that regulate the switch between adaptive and proapoptotic phases under stress...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621234/icarisid-ii-inhibits-the-proliferation-of-human-osteosarcoma-cells-by-inducing-apoptosis-and-cell-cycle-arrest
#5
Yuanyuan Tang, Mao Xie, Neng Jiang, Feifei Huang, Xiao Zhang, Ruishan Li, Jingjing Lu, Shijie Liao, Yun Liu
Icarisid II, one of the main active components of Herba Epimedii extracts, shows potent antitumor activity in various cancer cell lines, including osteosarcoma cells. However, the anticancer mechanism of icarisid II against osteosarcoma U2OS needs further exploration. This study aims to investigate further antitumor effects of icarisid II on human osteosarcoma cells and elucidate the underlying mechanism. We cultivated human osteosarcoma USO2 cells in vitro using different concentrations of icarisid II (0-30 µM)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28619845/the-prohibitin-binding-compound-fluorizoline-induces-apoptosis-in-chronic-lymphocytic-leukemia-cells-through-the-upregulation-of-noxa-and-synergizes-with-ibrutinib-aicar-or-venetoclax
#6
Ana M Cosialls, Helena Pomares, Daniel Iglesias-Serret, José Saura-Esteller, Sonia Núñez-Vázquez, Diana M González-Gironès, Esmeralda de la Banda, Sara Preciado, Fernando Albericio, Rodolfo Lavilla, Gabriel Pons, Eva M González-Barca, Joan Gil
Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In this study, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features, whereas normal T lymphocytes were less sensitive...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28619760/fbw7-dependent-mcl-1-degradation-mediates-the-anticancer-effect-of-hsp90-inhibitors
#7
Jingshan Tong, Shuai Tan, Zaneta Nikolovska-Coleska, Jian Yu, Fangdong Zou, Lin Zhang
Heat shock protein 90 (Hsp90) is widely overexpressed in cancer cells and necessary for maintenance of malignant phenotypes. Hsp90 inhibition induces tumor cell death through degradation of its client oncoproteins, and has shown promises in preclinical studies. However, the mechanism by which Hsp90 inhibitors kill tumor cells is not well understood. Biomarkers associated with differential sensitivity and resistance to Hsp90 inhibitors remain to be identified. In this study, we found that colorectal cancer (CRC) cells containing inactivating mutations of FBW7, a tumor suppressor and E3 ubiquitin ligase, are intrinsically insensitive to Hsp90 inhibitors...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28618955/oridonin-synergizes-with-nutlin-3-in-osteosarcoma-cells-by-modulating-the-levels-of-multiple-bcl-2-family-proteins
#8
Xiao-Hui Wang, Shu-Feng Zhang, Jun-Tao Bao, Fu-Yun Liu
The small-molecule inhibitors of p53-murine double minute 2 interaction, such as Nutlin-3, are effective against cancers bearing wild-type p53. However, murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells. To address this issue, we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells. We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1, but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28608415/crystal-structural-characterization-reveals-novel-oligomeric-interactions-of-human-voltage-dependent-anion-channel-1
#9
Toshiaki Hosaka, Masateru Okazaki, Tomomi Kimura-Someya, Yoshiko Ishizuka-Katsura, Kaori Ito, Shigeyuki Yokoyama, Kosuke Dodo, Mikiko Sodeoka, Mikako Shirouzu
Voltage-dependent anion channel 1 (VDAC1), which is located in the outer mitochondrial membrane, plays important roles in various cellular processes. For example, oligomerization of VDAC1 is involved in the release of cytochrome c to the cytoplasm, leading to apoptosis. However, it is unknown how VDAC1 oligomerization occurs in the membrane. In the present study, we determined high-resolution crystal structures of oligomeric human VDAC1 (hVDAC1) prepared by using an Escherichia coli cell-free protein synthesis system, which avoided the need for denaturation and refolding of the protein...
June 12, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28599419/a-conditionally-replicating-adenovirus-expressing-il-24-acts-synergistically-with-temozolomide-to-enhance-apoptosis-in-melanoma-cells-in-vitro
#10
Zhen Liang, Chun-Sheng Yang, Feng Gu, Lan-Sheng Zhang
Malignant melanoma is characterized by suppressed apoptosis in tumor cells and high levels of invasion. Temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and frequently. Therapeutic cytokines such as interleukin-24 (IL-24) and conditionally replicating adenoviruses have exhibited promising results as complementary therapies. Thus, the present study hypothesized that a conditionally replicating adenovirus expressing IL-24 combined with TMZ may exhibit increased antitumor activity compared with either treatment alone in melanoma A375 and M14 cell lines in vitro...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28594323/epistatic-mutations-in-puma-bh3-drive-an-alternate-binding-mode-to-potently-and-selectively-inhibit-anti-apoptotic-bfl-1
#11
Justin M Jenson, Jeremy A Ryan, Robert A Grant, Anthony Letai, Amy E Keating
Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs...
June 8, 2017: ELife
https://www.readbyqxmd.com/read/28588082/ire1%C3%AE-promotes-viral-infection-by-conferring-resistance-to-apoptosis
#12
Susan L Fink, Teshika R Jayewickreme, Ryan D Molony, Takao Iwawaki, Charles S Landis, Brett D Lindenbach, Akiko Iwasaki
The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. We found that Xbp1-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I IFN responses but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28586754/enantiomerically-pure-%C3%AE-dipeptide-derivative-induces-anticancer-activity-against-human-hormone-refractory-prostate-cancer-through-both-pi3k-akt-dependent-and-independent-pathways
#13
Mei-Ling Chan, Chia-Chun Yu, Jui-Ling Hsu, Wohn-Jenn Leu, She-Hung Chan, Lih-Ching Hsu, Shih-Ping Liu, Polina M Ivantcova, Özdemir Dogan, Stefan Bräse, Konstantin V Kudryavtsev, Jih-Hwa Guh
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure β-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586007/apg-1252-12a-induces-mitochondria-dependent-apoptosis-through-inhibiting-the-antiapoptotic-proteins-bcl-2-bcl-xl-in-hl-60-cells
#14
Jing Wang, Dajun Yang, Qiuyun Luo, Miaozhen Qiu, Lin Zhang, Baoxia Li, Haibo Chen, Hanjie Yi, Xianglei Yan, Shuxia Li, Jian Sun
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers...
June 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28581009/decoding-the-anticancer-activity-of-vo-clioquinol-compound-the-mechanism-of-action-and-cell-death-pathways-in-human-osteosarcoma-cells
#15
Ignacio E León, Paula Díez, Enrique J Baran, Susana B Etcheverry, Manuel Fuentes
Vanadium compounds were studied in recent years by considering them as a representative of a new class of non-platinum metal anticancer drugs. However, a few challenges still remain in the discovery of new molecular targets of these new metallodrugs. Studies on cell signaling pathways related to vanadium compounds have scarcely been reported and so far this information is highly critical for identifying novel targets that play a key role in the antitumor actions of vanadium complexes. This research deals with the alterations in the intracellular signaling pathways promoted by an oxovanadium(iv) complex with the clioquinol (5-chloro-7-iodo-8-quinolinol), VO(CQ)2, on a human osteosarcoma cell line (MG-63)...
June 5, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28580175/differential-cytokine-withdrawal-induced-death-sensitivity-of-effector-t-cells-derived-from-distinct-human-cd8-memory-subsets
#16
Sasha E Larsen, Kelsey Voss, Eric D Laing, Andrew L Snow
CD8(+) central memory (CM) and effector memory (EM) T-cell subsets exhibit well-established differences in proliferative and protective capacity after infectious challenge. However, their relative sensitivity to apoptosis has been largely overlooked, despite the importance of programmed cell death in regulating effector T-cell homeostasis. Here we demonstrate that primary human effector T cells derived from the CD8(+) EM subset exhibit significantly higher sensitivity to cytokine withdrawal-induced cell death (CWID), a critical intrinsic apoptosis program responsible for culling cells once an infection is cleared and interleukin-2 (IL-2) levels diminish...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28578655/potential-mechanisms-of-resistance-to-venetoclax-and-strategies-to-circumvent-it
#17
Stephen K Tahir, Morey L Smith, Paul Hessler, Lisa Roberts Rapp, Kenneth B Idler, Chang H Park, Joel D Leverson, Lloyd T Lam
BACKGROUND: Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges...
June 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28565798/pcsk9-regulates-apoptosis-in-human-lung-adenocarcinoma-a549-cells-via-endoplasmic-reticulum-stress-and-mitochondrial-signaling-pathways
#18
Xiaohui Xu, Yushang Cui, Lei Cao, Ye Zhang, Yan Yin, Xue Hu
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the subtilisin family of PCs that encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 in lung cancer cell apoptosis has remained elusive. In the present study, A549 human lung adenocarcinoma cells were transfected with PCSK9 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis. The results indicated that PCSK9 siRNA exhibited anti-tumor activity by inducing apoptosis as determined by a Cell Counting Kit-8 and Hoechst staining analysis...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28565770/dose-dependent-effect-of-curcuma-longa-for-the-treatment-of-parkinson-s-disease
#19
Xiao-Wei Ma, Rui-You Guo
Curcuma longa is a plant that belongs to the ginger family, Zingiberaceae. It has been used in Siddha medicine for thousands of years in Asia. Parkinson's disease (PD) is a degenerative disorder of the central nervous system that affects the motor system of the brain. Death of dopamine-producing cells in the substantia nigra leads to PD. Exposure to salsolinol, which is an endogenous neurotoxin, has been associated with damage to dopamine-producing cells. The present study assessed the toxicity of salsolinol in SH-SY5Y human neuroblastoma cells and subsequently investigated the neuroprotective potential of C...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28556798/loss-of-bax-by-mir-365-promotes-cutaneous-squamous-cell-carcinoma-progression-by-suppressing-apoptosis
#20
Liang Zhou, Ruirui Gao, Yinghui Wang, Meijuan Zhou, Zhenhua Ding
Pro-apoptotic BCL2 associated X (BAX) is traditionally thought to be regulated by anti-apoptotic BCL-2 family members, like BCL2-like 1 (BCL-XL), at the protein level. However, the posttranscriptional regulation of BAX is under explored. In this study, we identified BAX as the novel downstream target of miR-365, which is supported by gain- and loss-of-function studies of onco-miR-365. Loss of BAX by either RNA interference or highly-expressed miR-365 in cells of cutaneous squamous cell carcinoma (CSCC) enhanced the tumor resistance against apoptosis, while repressing cell proliferation, migration, and invasiveness...
May 30, 2017: International Journal of Molecular Sciences
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