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https://www.readbyqxmd.com/read/28732245/interleukin-4-receptor-targeted-delivery-of-bcl-xl-sirna-sensitizes-tumors-to-chemotherapy-and-inhibits-tumor-growth
#1
Padmanaban Guruprasath, Jihoon Kim, Gowri Rangaswamy Gunassekaran, Lianhua Chi, Soyoun Kim, Rang-Woon Park, Sang-Hyun Kim, Moon-Chang Baek, Sang Mun Bae, Sang-Yeob Kim, Dong-Kyu Kim, In-Kyu Park, Won-Jong Kim, Byungheon Lee
IL-4 receptor (IL-4R) is commonly up-regulated on tumor cells, and interactions between the receptor and Interleukin-4 (IL-4) can induce the expression of anti-apoptotic proteins, including Bcl-xL. This contributes to tumor cell survival and their resistance to chemotherapy. In this study, we exploited IL-4R-targeted delivery of Bcl-xL siRNA to IL-4R-expressing tumor cells in order to sensitize them to chemotherapy. To target IL-4R, an IL-4R-binding peptide, IL4RPep-1, was attached to branched polyethyleneimine-superparamagnetic iron oxide nanoparticles (BPEI-SPION)...
July 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28731183/paeoniflorin-exerts-neuroprotective-effects-against-glutamate%C3%A2-induced-pc12-cellular-cytotoxicity-by-inhibiting-apoptosis
#2
Ahong Chen, Hongyun Wang, Yuqin Zhang, Xiaoying Wang, Lishuang Yu, Wen Xu, Wei Xu, Yu Lin
Paeoniflorin (PF) is an active ingredient of Radix Paeoniae, which is known to exert neuroprotective effects. However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade response. This study aimed to investigate neuroprotective effects of PF against glutamate‑induced PC12 cellular cytotoxicity and to determine whether these effects are mediated via the inhibition of apoptosis in vitro and the activity of mitochondrial apoptosis-associated proteins in PC12 cells...
July 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28731164/active-targeting-co-delivery-system-based-on-hollow-mesoporous-silica-nanoparticles-for-antitumor-therapy-in-ovarian-cancer-stem-like-cells
#3
Xin Guo, Nan Guo, Jianwen Zhao, Yunlang Cai
The combination of nanocarriers and chemotherapy drugs can release the chemotherapy drugs to the tumor tissue, which can enhance the antitumor effect and reduce the adverse reactions at the same time. In this study, a co-delivery system based on hollow mesoporous silica nanoparticles (HMSN) was developed and characterized. We also investigated the in vitro effect of this system on CD117+CD44+A2780 cell line. HMSN was selected as the nanocarrier, with -COOH modified on the surface and doxorubicin (DOX), NVP-AEW 541 (NVP) loaded inside...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28730778/study-on-the-effect-of-integrin-%C3%AE-%C3%AE-%C3%AE-6-on-the-proliferation-and-apoptosis-of-thyroid-carcinoma-cells
#4
Zhilong Tian, Hailin Xi, Xiaokai Wang, Su Feng, Gaolei Jia
PURPOSE: To study the effect of integrin αvβ6 on the proliferation and apoptosis of thyroid carcinoma cells. METHODS: The experiment was conducted on 3 groups : the control group, the positive observation group (in which the ανβ6 on the surface of the thyroid carcinoma cell line SW579 was blocked by monoclonal antibody 10D5) and the negative observation group (in which the ανβ6 was dealt with the negative placebo of 10D5-the IgG2a). Cell proliferation was detected by MTT assay, apoptosis by flow cytometry and the protein levels in Caspase-3, CyclinB1 and Bcl-xl as well as the protein levels in ERK, p-ERK, JNK, p-JNK, p38 and p-p38 were detected by Western blot...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729093/pim-kinases-1-2-and-3-in-intracellular-lif-signalling-proliferation-and-apoptosis-in-trophoblastic-cells
#5
Stella Mary Photini, Wittaya Chaiwangyen, Maja Weber, Boodor Al-Kawlani, Rodolfo R Favaro, Udo Jeschke, Ekkehard Schleussner, Diana M Morales-Prieto, Udo R Markert
Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3...
July 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28728173/glucocorticoid-induced-leucine-zipper-protects-the-retina-from-light-induced-retinal-degeneration-by-inducing-bcl-xl-in-rats
#6
Ruiping Gu, Wenyi Tang, Boya Lei, Xinyi Ding, Cheng Jiang, Gezhi Xu
Purpose: The aim of the present study was to investigate the neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ) in a light-induced retinal degeneration model and to explore the underlying mechanisms. Methods: Intravitreal injection of recombinant GILZ-overexpressing lentivirus (OE-GILZ-rLV) and short hairpin RNA targeting GILZ recombinant lentivirus (shRNA-GILZ-rLV) was performed to up- and downregulate retinal GILZ, respectively. Three days after stable transduction, rats were exposed to continuous bright light (5000 lux) for 2 days...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28724935/histone-deacetylase-3-is-required-for-inkt-cell-development
#7
Puspa Thapa, Sinibaldo Romero Arocha, Ji Young Chung, Derek B Sant'Angelo, Virginia Smith Shapiro
NKT cells are a distinct subset that have developmental requirements that often differ from conventional T cells. Here, we show that NKT-specific deletion of Hdac3 results in a severe reduction in the number of iNKT cells, particularly of NKT1 cells. In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 cells. Hdac3-deficient iNKT cells have increased cell death that is not rescued by transgenic expression of Bcl-2 or Bcl-xL. Hdac3-deficient iNKT cells have less Cyto-ID staining and lower LC3A/B expression, indicative of reduced autophagy...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723693/upregulation-of-microrna-876-induces-endothelial-cell-apoptosis-by-suppressing-bcl-xl-in-development-of-atherosclerosis
#8
Kaicheng Xu, Peng Liu, Yue Zhao
BACKGROUND/AIMS: The injury and apoptotic cell death of endothelial cells hallmark the development of atherosclerosis (AS), characterized by dysregulation of lipid homeostasis, immune responses, and formation of coronary plaques. However, the mechanisms underlying the initiation of endothelial cell apoptosis remain ill-defined. Recent evidence suggests a role of microRNAs in the processes of AS-associated endothelial cell apoptosis. Thus, we studied this question in the current study...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28714901/selenium-containing-polysaccharide-protein-complex-in-se-enriched-ulva-fasciata-induces-mitochondria-mediated-apoptosis-in-a549-human-lung-cancer-cells
#9
Xian Sun, Yu Zhong, Hongtian Luo, Yufeng Yang
The role of selenium (Se) and Ulva fasciata as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical, and clinical studies. In this study, Se-containing polysaccharide-protein complex (Se-PPC), a novel organoselenium compound, a Se-containing polysaccharide-protein complex in Se-enriched Ulva fasciata, is a potent anti-proliferative agent against human lung cancer A549 cells. Se-PPC markedly inhibited the growth of cancer cells via induction of apoptosis which was accompanied by the formation of apoptotic bodies, an increase in the population of apoptotic sub-G1 phase cells, upregulation of p53, and activation of caspase-3 in A549 cells...
July 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28714512/inhibition-of-stat3-signaling-pathway-by-ursolic-acid-suppresses-growth-of-hepatocellular-carcinoma
#10
Tianshu Liu, Haiyan Ma, Wei Shi, Jialin Duan, Yina Wang, Cuntai Zhang, Chenglong Li, Jiayuh Lin, Sheng Li, Jiagao Lv, Li Lin
The signal transducer and activator of transcription 3 (STAT3) has been found to be constitutively active in liver cancer. There is no STAT3 inhibitors approved to be used clinically for the treatment or prevention of liver cancer. Some dietary compounds including ursolic acid (UA) have been reported to inhibit the growth of cancer cells. However, whether UA could inhibit STAT3 phosphorylation in hepatocellular carcinoma has not been reported. The inhibitory effects of UA on STAT3 phosphorylation, along with cell viability, migration, colony formation in vitro, as well as tumor growth in vivo were examined in human liver cancer cell lines...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28714472/targeting-the-differential-addiction-to-anti-apoptotic-bcl-2-family-for-cancer-therapy
#11
Akane Inoue-Yamauchi, Paul S Jeng, Kwanghee Kim, Hui-Chen Chen, Song Han, Yogesh Tengarai Ganesan, Kota Ishizawa, Sylvia Jebiwott, Yiyu Dong, Maria C Pietanza, Matthew D Hellmann, Mark G Kris, James J Hsieh, Emily H Cheng
BCL-2 family proteins are central regulators of mitochondrial apoptosis and validated anti-cancer targets. Using small cell lung cancer (SCLC) as a model, we demonstrated the presence of differential addiction of cancer cells to anti-apoptotic BCL-2, BCL-XL or MCL-1, which correlated with the respective protein expression ratio. ABT-263 (navitoclax), a BCL-2/BCL-XL inhibitor, prevented BCL-XL from sequestering activator BH3-only molecules (BH3s) and BAX but not BAK. Consequently, ABT-263 failed to kill BCL-XL-addicted cells with low activator BH3s and BCL-XL overabundance conferred resistance to ABT-263...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28714369/sporamin-induces-apoptosis-and-inhibits-nf-%C3%AE%C2%BAb-activation-in-human-pancreatic-cancer-cells
#12
Cuijuan Qian, Xiaoying Chen, Yongxiao Qi, Sheng Zhong, Xinyan Gao, Wenjun Zheng, Zhixiang Mao, Jun Yao
Sporamin, a Kunitz-type trypsin inhibitor (TI) from sweet potato tuberous roots, has demonstrated anti-tumor activity through poorly defined mechanisms. Furthermore, the effects of sporamin on pancreatic cancer have not been explored. Herein, we studied the effects of sporamin on two human pancreatic cancer cell lines, PANC-1 and BxPC-3. Sporamin significantly inhibited the cell viability and proliferation activity and induced apoptosis in PANC-1 and BxPC-3 cells. Consistently, in sporamin-treated PANC-1 and BxPC-3 cells, the anti-apoptotic proteins Bcl-2 and Bcl-XL were downregulated and the pro-apoptotic protein Bax was upregulated...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28713944/truncated-apolipoprotein-c-i-induces-apoptosis-in-neuroblastoma-by-activating-caspases-in-the-extrinsic-and-intrinsic-pathways
#13
Fei Guo, Wei Zhao, Lin Yang, Yang Yang, Saiqi Wang, Yingjun Wang, Zhaoming Li, Jiaxiang Wang
Truncated apolipoprotein C-I is a post-translationally modified protein characterized by the loss of threonine and proline residues from the N-terminus of the mature peptide. The truncated peptide is involved in many physiological and pathological processes in vivo and is related to malignant diseases. The aim of the present study was to assess the effects of the truncated peptide on tumorigenesis in neuroblastoma. The truncated peptide was chemically synthesized, and a signal peptide was used as the negative control...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713162/abt-263-induces-g1-g0-phase-arrest-apoptosis-and-autophagy-in-human-esophageal-cancer-cells-in-vitro
#14
Qing-Huan Lin, Fu-Chang Que, Chun-Ping Gu, De-Sheng Zhong, Dan Zhou, Yi Kong, Le Yu, Shu-Wen Liu
Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28712306/targeting-intrinsic-apoptosis-and-other-forms-of-cell-death-by-bh3-mimetics-in-glioblastoma
#15
Georg Karpel-Massler, Chiaki Tsuge Ishida, Yiru Zhang, Marc-Eric Halatsch, M-Andrew Westhoff, Markus D Siegelin
Novel approaches to treat malignant brain tumors are necessary since these neoplasms still display an unfavorable prognosis. Areas covered: In this review, the authors summarize and analyze recent preclinical data that suggest that targeting intrinsic apoptosis may be a suitable strategy for the treatment of malignant gliomas. They focus on the anti-apoptotic Bcl-2 family members of proteins and the recent drug developments in that field with a special focus on BH3-mimetics. With the discovery of BH3-mimetics that interfere with anti-apoptotic Bcl-2 family members in the low nanomolar range significant excitement has been generated towards these class of inhibitors, such as ABT-737, ABT-263 and the most recent successor, ABT-199 which is most advanced with respect to clinical application...
July 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28711932/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#16
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711493/anti-cancer-effect-of-oncolytic-adenovirus-armed-shrna-targeting-mycn-gene-on-doxorubicin-resistant-neuroblastoma-cells
#17
Yuan Li, Baobiao Zhuo, Yiyu Yin, Tao Han, Shixian Li, Zhengwei Li, Jian Wang
Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#18
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28706229/quantitative-interactome-of-a-membrane-bcl-2-network-identifies-a-hierarchy-of-complexes-for-apoptosis-regulation
#19
Stephanie Bleicken, Annika Hantusch, Kushal Kumar Das, Tancred Frickey, Ana J Garcia-Saez
The Bcl-2 proteins form a complex interaction network that controls mitochondrial permeabilization and apoptosis. The relative importance of different Bcl-2 complexes and their spatio-temporal regulation is debated. Using fluorescence cross-correlation spectroscopy to quantify the interactions within a minimal Bcl-2 network, comprised by cBid, Bax, and Bcl-xL, we show that membrane insertion drastically alters the pattern of Bcl-2 complexes, and that the C-terminal helix of Bcl-xL determines its binding preferences...
July 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28706161/the-molecular-mechanisms-of-chemoresistance-in-cancers
#20
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
July 6, 2017: Oncotarget
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