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PARP inhibitors

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https://www.readbyqxmd.com/read/29035012/regulatory-effects-of-black-rice-extract-on-helicobacter-pylori-infection-induced-apoptosis
#1
Sa-Hyun Kim, Min Ho Lee, Min Park, Hyun Jun Woo, Yoon Suk Kim, Nagendran Tharmalingam, Woo-Duck Seo, Jong-Bae Kim
SCOPE: Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major component. In this study, we found that BRE inhibited the mRNA and protein expression of genes encoding cytotoxin-associated protein A (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain. METHODS AND RESULTS: We performed RT-PCR and western blotting to show that BRE inhibited the mRNA and protein expression of SecA. Because SecA is involved in VacA export in bacteria, our result suggested a positive correlation between BRE-induced inhibition of secA expression and VacA secretion...
October 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29031204/ginkgetin-inhibits-growth-of-breast-carcinoma-via-regulating-mapks-pathway
#2
Jun Cao, Chuang Tong, Yanyan Liu, Jianguo Wang, Xiaoyan Ni, Mao-Ming Xiong
The purpose of present study was to investigate anti-tumor activity of Ginkgetin (GK) and its mechanism of action in breast cancer. The effects of GK on growth of human breast cancer cell lines MDA-MB-231, BT-474 and MCF-7 were examined by MTT assay. Cells apoptosis in MCF-7 cells were analyzed by TUNEL staining and annexin-V and propidium iodide double staining. The effects of GK on expression of apoptotic associated proteins and mitogen-activated protein kinases (MAPKs) were determined by western blotting...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29031068/platinum-iv-prodrugs-multiply-targeting-genomic-dna-histone-deacetylases-and-parp-1
#3
Zichen Xu, Weiwei Hu, Zhimei Wang, Shaohua Gou
Several Pt(IV) prodrugs containing SAA, a histone deacetylases inhibitor, were designed and prepared for multiply targeting genomic DNA, histone deacetylases and PARP-1. The resulting Pt(IV) prodrug had significantly strong antiproliferative activity against the tested cancer cell lines, especially SAA1, derived from the conjugation of cisplatin and SAA, had potent ability to overcome cisplatin resistance. Under the combined action of DNA platination and inhibition of HDACs and PARP-1 activity, the cytotoxic activity of SAA1 was 174-fold higher than cisplatin against cisplatin-resistant SGC7901/CDDP cancer cells...
October 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29027939/nicotine-component-of-cigarette-smoke-extract-cse-decreases-the-cytotoxicity-of-cse-in-beas-2b-cells-stably-expressing-human-cytochrome-p450-2a13
#4
Minghui Ji, Yudong Zhang, Na Li, Chao Wang, Rong Xia, Zhan Zhang, Shou-Lin Wang
Cytochrome P450 2A13 (CYP2A13), an extrahepatic enzyme mainly expressed in the human respiratory system, has been reported to mediate the metabolism and toxicity of cigarette smoke. We previously found that nicotine inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by CYP2A13, but its influence on other components of cigarette smoke remains unclear. The nicotine component of cigarette smoke extract (CSE) was separated, purified, and identified using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), splitting CSE into a nicotine section (CSE-N) and nicotine-free section (CSE-O)...
October 13, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29025293/berberine-induces-apoptotic-cell-death-via-activation-of-caspase-3-and-8-in-hl-60-human-leukemia-cells-nuclear-localization-and-structure-activity-relationships
#5
Shinya Okubo, Takuhiro Uto, Aya Goto, Hiroyuki Tanaka, Tsuyoshi Nishioku, Katsushi Yamada, Yukihiro Shoyama
Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29017950/the-synergistic-effects-of-valproic-acid-and-fluvastatin-on-apoptosis-induction-in-glioblastoma-multiforme-cell-lines
#6
Yung-Lung Chang, Li-Chun Huang, Ying-Chuan Chen, Yi-Wen Wang, Dueng-Yuan Hueng, Shih-Ming Huang
Glioblastoma multiforme (GBM) is the most common primary central nervous system malignant tumor. It responds poorly to standard therapies, such as surgical resection, radiation therapy and chemotherapy. Many chemotherapeutic drugs are focused on apoptosis induction and radiation sensitivity. Inhibition of histone acetylation via histone deacetylase inhibitor (HDACI) is one such strategy. Statins (or 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are classical drugs used to lower cholesterol but also inhibitors of histone deacetylation activity...
October 7, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28994564/targeted-therapy-for-ovarian-cancer-the-rapidly-evolving-landscape-of-parp-inhibitor-use
#7
Christine Walsh
INTRODUCTION: PARP (poly(ADP-ribose) polymerase) inhibitors are a targeted therapy option for ovarian cancer. The goal of this review was to organize and summarize the clinical trials evaluating PARP inhibitor therapy in ovarian cancer as monotherapy, maintenance therapy after partial or complete remission to therapy or as a part of a combination regimen. EVIDENCE ACQUISITION: PubMed, ClinicalTrials.gov, data from the United States Food and Drug Administration (US FDA) and proceedings from scientific conferences were searched for published and unpublished data pertaining to clinical trials and approvals of PARP inhibitor use in ovarian cancer...
October 9, 2017: Minerva Ginecologica
https://www.readbyqxmd.com/read/28994419/targeted-therapy-ariel3-broad-benefit-of-parp-inhibitors-in-ovarian-cancer
#8
David Killock
No abstract text is available yet for this article.
October 10, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28993682/olaparib-modulates-dna-repair-efficiency-sensitizes-cervical-cancer-cells-to-cisplatin-and-exhibits-anti-metastatic-property
#9
Chandra Bhushan Prasad, Shyam Babu Prasad, Suresh Singh Yadav, Laxmi Kant Pandey, Sunita Singh, Satyajit Pradhan, Gopeshwar Narayan
PARP1 trapping at DNA lesion by pharmacological inhibitors has been exploited in several cancers exhibiting defects in DNA repair mechanisms. PARP1 hyperactivation is involved in therapeutic resistance in multiple cancers. The role of PARP1 in cervical cancer (CC) resistance and implication of PARP inhibitor is yet to be elucidated. Our data demonstrates significantly higher expression of PARP1 in primary cervical tumors and CC cell lines SiHa and ME180. Upon cisplatin treatment CC cells display significant overexpression of PARP1 and its hyperactivation...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993192/up-regulation-of-rip3-alleviates-cervical-cancer-progression-through-inducing-necroptosis
#10
Dong-Li Zhang, Gui-Xia Sun, Jun Tian, Hong-Xia Zhang
Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an important part of the cellular machinery, executing programmed necroptosis. However, the biological role and clinical significance of RIP3 in cervical cancer remains to be further elucidated. Here, we reported that RIP3 was expressed lowly in cervical cancer cell lines and clinical cervical tumor samples, along with the reduction of receptor-interacting protein 1 (RIP1) and p-mixed lineage kinase domain-like protein (MLKL). Further, we found that over-expressing RIP3 suppressed the proliferation and tumorigenicity of cervical cancer cells both in vitro and in vivo...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28991194/parp1-in-carcinomas-and-parp1-inhibitors-as-antineoplastic-drugs
#11
REVIEW
Luyao Wang, Chao Liang, Fangfei Li, Daogang Guan, Xiaoqiu Wu, Xuekun Fu, Aiping Lu, Ge Zhang
Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis...
October 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28986307/interleukin-1%C3%AE-and-tumor-necrosis-factor-%C3%AE-augment-acidosis-induced-rat-articular-chondrocyte-apoptosis-via-nuclear-factor-kappab-dependent-up-regulation-of-asic1a-channel
#12
Ren-Peng Zhou, Bei-Bei Dai, Ya-Ya Xie, Xiao-Shan Wu, Zhi-Sen Wang, Yue Li, Zhi-Qiang Wang, Sheng-Qin Zu, Jin-Fang Ge, Fei-Hu Chen
The acute-phase proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1β and TNF-α in acid-induced apoptosis of chondrocytes remain unclear...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28984489/directing-the-use-of-ddr-kinase-inhibitors-in-cancer-treatment
#13
Inger Brandsma, Emmy D G Fleuren, Chris T Williamson, Christopher J Lord
Introduction Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different PARP inhibitors for the treatment of ovarian cancer provides the impetus for further developing targeted inhibitors of many of the kinases involved in the DDR, including inhibitors of ATR, ATM, CHEK1, CHEK2, DNAPK and WEE1. Areas covered We summarise the current stage of development of these novel DDR kinase inhibitors, and describe which predictive biomarkers might be exploited to direct their clinical use...
October 6, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28981630/the-jak-stat3-signaling-pathway-mediates-inhibition-of-host-cell-apoptosis-by-chlamydia-psittaci-infection
#14
Yuanbin Sun, Peng Zhou, Shenghua Chen, Chunsheng Hu, Qinqin Bai, Haiying Wu, Yuyu Chen, Pufan Zhou, Xindian Zeng, Ziqing Liu, Lili Chen
The JAK-STAT3 signaling pathway is a key regulator of cell growth, motility, migration, invasion and apoptosis in mammalian cells. Infection with intracellular pathogens of the genus Chlamydia can inhibit host cell apoptosis, and here we asked whether the JAK-STAT3 pathway participates in chlamydial anti-apoptotic activity. We found that, compared with uninfected cells, levels of JAK1 and STAT3 mRNA as well as total and phosphorylated JAK1 and STAT3 protein, were significantly increased in C. psittaci-infected HeLa cells...
August 3, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28981117/trehalose-ameliorates-oxidative-stress-mediated-mitochondrial-dysfunction-and-er-stress-via-selective-autophagy-stimulation-and-autophagic-flux-restoration-in-osteoarthritis-development
#15
Qian Tang, Gang Zheng, Zhenhua Feng, Yu Chen, Yiting Lou, Chenggui Wang, Xiaolei Zhang, Yu Zhang, Huazi Xu, Ping Shang, Haixiao Liu
Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28981112/berberine-induces-oxidative-dna-damage-and-impairs-homologous-recombination-repair-in-ovarian-cancer-cells-to-confer-increased-sensitivity-to-parp-inhibition
#16
Dong Hou, Guangwei Xu, Caibo Zhang, Boxuan Li, Junchao Qin, Xiaohe Hao, Qiao Liu, Xiyu Zhang, Jinsong Liu, Jianjun Wei, Yaoqin Gong, Zhaojian Liu, Changshun Shao
Many cancer drugs exert their therapeutic effect by inducing oxidative stress in the cancer cells. Oxidative stress compromises cell survival by inflicting lesions in macromolecules like DNA. Cancer cells rely on enhanced antioxidant metabolism and increased DNA repair function to survive oxidative assault. PARP1, a protein that senses DNA-strand breaks and orchestrates their repair, has an important role in the repair of oxidative DNA damage. Berberine, an alkaloid compound present in many herbal plants, is capable of inducing oxidative DNA damage and downregulating homologous recombination repair (HRR) in cancer cells...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28979099/investigating-isoquinoline-derivatives-for-inhibition-of-inhibitor-of-apoptosis-proteins-for-ovarian-cancer-treatment
#17
Chen Chen, Jie Wu, Pengfei Zhu, Congjian Xu, Liangqing Yao
OBJECTIVE: To discover novel isoquinoline derivatives for inhibition of inhibitor of apoptosis proteins (IAP) for the treatment of ovarian cancer. METHODS: We first synthesized 533 isoquinoline derivatives, and screened them using CCK-8 to measure their antiproliferative activity. These compounds were further tested by Hoechst staining and flow cytometric analysis to assess proapoptotic activity. The in vivo antitumor efficacy and safety of the screened compounds were evaluated on the xenograft mouse model...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28978184/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#18
REVIEW
Paul Lesueur, François Chevalier, Jean-Baptiste Austry, Waisse Waissi, Hélène Burckel, Georges Noël, Jean-Louis Habrand, Yannick Saintigny, Florence Joly
BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978150/parp-inhibitors-protect-against-sex-and-aag-dependent-alkylation-induced-neural-degeneration
#19
Mariacarmela Allocca, Joshua J Corrigan, Kimberly R Fake, Jennifer A Calvo, Leona D Samson
Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type and Aag-transgenic (AagTg) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975372/t-buooh-induces-ferroptosis-in-human-and-murine-cell-lines
#20
Christine Wenz, Dagmar Faust, Berenike Linz, Christian Turmann, Teodora Nikolova, John Bertin, Peter Gough, Peter Wipf, Anna Sophia Schröder, Stefan Krautwald, Cornelia Dietrich
Reactive oxygen species (ROS)-induced apoptosis has been extensively studied. Increasing evidence suggests that ROS, for instance, induced by hydrogen peroxide (H2O2), might also trigger regulated necrotic cell death pathways. Almost nothing is known about the cell death pathways triggered by tertiary-butyl hydroperoxide (t-BuOOH), a widely used inducer of oxidative stress. The lipid peroxidation products induced by t-BuOOH are involved in the pathophysiology of many diseases, such as cancer, cardiovascular diseases, or diabetes...
October 3, 2017: Archives of Toxicology
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