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https://www.readbyqxmd.com/read/29453076/development-of-novel-synthesized-phthalazinone-based-parp-1-inhibitors-with-apoptosis-inducing-mechanism-in-lung-cancer
#1
Hadia Almahli, Elie Hadchity, Maiy Y Jaballah, Racha Daher, Hazem A Ghabbour, Maha M Kabil, Nasser S Al-Shakliah, Wagdy M Eldehna
Herein we report the synthesis of two series of 4-phenylphthalazin-1-ones 11a-i and 4- benzylphthalazin-1-ones 16a-h as anti-lung adenocarcinoma agents with potential inhibitory activity against PARP-1. All the newly synthesized phthalazinones were evaluated for their anti-proliferative activity against A549 lung carcinoma cell line. Phthalazinones 11c-i and 16b, c showed significant cytotoxic activity against A549 cells at different concentrations (0.1, 1 and 10 μM) for two time intervals (24 h and 48 h)...
February 7, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29446234/a-natural-antioxidant-tannic-acid-mitigates-iron-overload-induced-hepatotoxicity-in-swiss-albino-mice-through-ros-regulation
#2
Tapasree Basu, Sourav Panja, Anil Khushalrao Shendge, Abhishek Das, Nripendranath Mandal
Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation...
February 15, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29443732/curcumin-induces-apoptosis-and-inhibits-proliferation-in-infantile-hemangioma-endothelial-cells-via-downregulation-of-mcl-1-and-hif-1%C3%AE
#3
Suhui Lou, Yanfang Wang, Zujiang Yu, Kelei Guan, Quancheng Kan
BACKGROUND: Curcumin has been used as an alternative medicine for the treatment of infantile hemangiomas (IHs); however, the mechanism underlying the effectiveness of curcumin in IHs remains largely unclear. METHODS: In this study, we isolated primary human hemangioma endothelial cells (HemECs) from fresh surgical specimens of 3 patients. We treated HemECs by curcumin and investigated the alterations in proliferative and apoptotic signaling pathways with cell counting kit-8, flow cytometry, western blotting, immunofluorescence, and real-time polymerase chain reaction...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29436674/the-targeted-inhibition-of-hsp90-by-a-synthetic-small-molecule-dpide-offers-an-effective-treatment-strategy-against-tnbcs
#4
Yong Jin Oh, Sun You Park, Young Ho Seo
Triple-negative breast cancers (TNBCs) are the most aggressive and metastatic subtype of breast cancers and exhibit poor clinical outcome due to the lack of drug target receptors such as estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (Her2). The limited effectiveness of therapeutic options and the poor prognosis of TNBC patients emphasize the urgent need for identifying new therapeutic agents. In this regard, heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of TNBCs...
February 7, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29435178/inhibition-of-the-mek-erk-pathway-augments-nab-paclitaxel-based-chemotherapy-effects-in-preclinical-models-of-pancreatic-cancer
#5
Niranjan Awasthi, Sheena Monahan, Alexis Stefaniak, Margaret A Schwarz, Roderich E Schwarz
Nab-paclitaxel (NPT) combination with gemcitabine (Gem) represents the standard chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Genetic alterations of the RAS/RAF/MEK/ERK (MAPK) signaling pathway yielding constitutive activation of the ERK cascade have been implicated as drivers of PDAC. Inhibition of downstream targets in the RAS-MAPK cascade such as MEK remains a promising therapeutic strategy. The efficacy of trametinib (Tra), a small molecule inhibitor of MEK1/2 kinase activity, in combination with nab-paclitaxel-based chemotherapy was evaluated in preclinical models of PDAC...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435156/cis-trimethoxy-resveratrol-induces-intrinsic-apoptosis-via-prometaphase-arrest-and-prolonged-cdk1-activation-pathway-in-human-jurkat-t-cells
#6
Chae Eun Kim, Do Youn Jun, Jong-Sik Kim, Young Ho Kim
Cis-trimethoxy resveratrol (cis-3M-RES) induced dose-dependent cytotoxicity and apoptotic DNA fragmentation in Jurkat T cell clones (JT/Neo); however, it induced only cytostasis in BCL-2-overexpressing cells (JT/BCL-2). Treatment with 0.25 μM cis-3M-RES induced G2/M arrest, BAK activation, Δψm loss, caspase-9 and caspase-3 activation, and poly (ADP-ribose) polymerase (PARP) cleavage in JT/Neo cells time-dependently but did not induce these events, except G2/M arrest, in JT/BCL-2 cells. Moreover, cis-3M-RES induced CDK1 activation, BCL-2 phosphorylation at Ser-70, MCL-1 phosphorylation at Ser-159/Thr-163, and BIM (BIMEL and BIML) phosphorylation irrespective of BCL-2 overexpression...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435141/induction-of-endoplasmic-reticulum-stress-and-mitochondrial-dysfunction-dependent-apoptosis-signaling-pathway-in-human-renal-cancer-cells-by-norcantharidin
#7
Min-Hua Wu, Hui-Ling Chiou, Chu-Liang Lin, Ching-Yi Lin, Shun-Fa Yang, Yi-Hsien Hsieh
Previous studies reported that norcantharidin (NCTD) has anti-tumor effects. We investigated the antitumor effects and underlying mechanism of NCTD on human renal cancer in vitro and in vivo. NCTD significantly decreased renal cancer cell viability by induction of apoptosis, as determined by the MTT assay and annexin V/PI staining. NCTD treatment of 786-O and A-498 cells altered the expression of caspase family proteins and PARP. Moreover, NCTD induced mitochondrial depolarization, which was accompanied by an increased level of Bax and decreased levels of Bcl-2 and Mcl-1...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434958/anticancer-effects-of-10-hydroxycamptothecin-induce-apoptosis-of-human-osteosarcoma-through-activating-caspase-3-p53-and-cytochrome-c-pathways
#8
Xiong Min, Han Heng, Hua-Long Yu, Mao Dan, Chen Jie, Yun Zeng, He Ning, Zhi-Gang Liu, Zhi-Yong Wang, Wang Lin
In order to evaluate the anticancer effect of 10-hydroxycamptothecin (HCPT) in terms of inducing the apoptosis of human osteosarcoma cells, its apoptosis-inducing molecular mechanisms were investigated. In the present study, the anticancer effects of HCPT were revealed to result in suppressed cell viability, increased cytotoxicity, the induction of apoptosis and an augmented apoptotic nucleolus of human osteosarcoma cells. MG-63 cells were cultured with HCPT (0, 20, 40 and 80 nM) for 24 and 48 h. An MTT assay and a lactate dehydrogenase assay were used to analyze the anticancer effect of HCPT on cell viability and cytotoxicity in MG-63 cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434894/down-expression-of-poly-adp-ribose-polymerase-in-p53-regulated-pancreatic-cancer-cells
#9
Zhenyu Hou, Yunfeng Cui, Huizhi Xing, Xiaoyan Mu
The present study investigated whether poly(ADP-ribose) polymerase (PARP) has an effect on p53-regulated pancreatic cancer. The results of the present study demonstrated that the expression of PARP affects proliferation and apoptosis of pancreatic cancer cells. Olaparib was used to suppress the expression level of PARP-1 in PanC-1 cells. Decreased expression of PARP-1 suppressed cell proliferation and induced apoptosis of PanC-1 cells when compared with controls. Furthermore, decreased expression of PARP-1 resulted in decreased levels of pro-caspase-3 expression, increased caspase-3 activity, suppressed B-cell lymphoma 2 (Bcl-2) protein expression and increased p53 protein expression in PanC-1 cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433680/cyclocommunol-induces-apoptosis-in-human-oral-squamous-cell-carcinoma-partially-through-a-mcl-1-dependent-mechanism
#10
Jing-Ru Weng, Li-Yuan Bai, Horng-Huey Ko, Yi-Tung Tsai
BACKGROUND: Crude extract of breadfruit has been reported to have antitumor activity against various cancer cell lines with unknown mechanism. PURPOSE: This study aims to investigate the proapoptotic effect of cyclocommunol (CYC), a prenylflavonoid from breadfruit, in two oral squamous cell carcinoma (OSCC) cell lines, SCC2095 and Ca922. METHODS: The antiproliferative effects of CYC were assessed by MTT assays and PI/annexin V analysis. SCC2095 cells were transiently transfected with Mcl-1 plasmid in overexpression experiment...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29432993/oridonin-inhibits-oral-cancer-growth-and-pi3k-akt-signaling-pathway
#11
Jing Yang, Xianyue Ren, Liping Zhang, Yuanyuan Li, Bin Cheng, Juan Xia
Oridonin, a bioactive diterpenoid purified from Rabdosia rubescens, has been shown to possess anticancer capacity in several cancer types. However, its effects on oral squamous cell carcinoma (OSCC) cells remain unclear. This study aimed to investigate the anticancer ability of oridonin in OSCC cells, including proliferation, apoptosis and underlying mechanisms using the OSCC cell lines, UM1 and SCC25. The results showed that oridonin not only inhibited proliferation and clonal formation but also induced G2/M cell cycle arrest and apoptosis in UM1 and SCC25 cells in a dose-dependent manner...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29432837/vitamin-k2-a-menaquinone-present-in-dairy-products-targets-castration-resistant-prostate-cancer-cell-line-by-activating-apoptosis-signaling
#12
Subramanyam Dasari, Angela Lincy Prem Antony Samy, Andre Kajdacsy-Balla, Maarten C Bosland, Gnanasekar Munirathinam
The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC ® CRL-2876™) which was established from a vertebral bone metastasis from a patient with hormone refractory prostate cancer. Our data showed that VK2 significantly inhibited CRPC VCaP cell proliferation in a dosedependent manner at 48 h treatment in vitro. In addition, VK2 reduced the migration potential of VCaP cells and inhibited anchorage-independent growth of these cells...
February 9, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29432179/parp-1-dependent-recruitment-of-cold-inducible-rna-binding-protein-promotes-double-strand-break-repair-and-genome-stability
#13
Jung-Kuei Chen, Wen-Ling Lin, Zhang Chen, Hung-Wen Liu
Maintenance of genome integrity is critical for both faithful propagation of genetic information and prevention of mutagenesis induced by various DNA damage events. Here we report cold-inducible RNA-binding protein (CIRBP) as a newly identified key regulator in DNA double-strand break (DSB) repair. On DNA damage, CIRBP temporarily accumulates at the damaged regions and is poly(ADP ribosyl)ated by poly(ADP ribose) polymerase-1 (PARP-1). Its dissociation from the sites of damage may depend on its phosphorylation status as mediated by phosphatidylinositol 3-kinase-related kinases...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29431122/poly-adp-ribose-polymerase-1-regulates-fibroblast-activation-in-systemic-sclerosis
#14
Yun Zhang, Sebastian Pötter, Chih-Wei Chen, Ruifang Liang, Kolja Gelse, Ingo Ludolph, Raymund E Horch, Oliver Distler, Georg Schett, Jörg H W Distler, Clara Dees
OBJECTIVES: The enzyme poly(ADP-ribose) polymerase-1 (PARP-1) transfers negatively charged ADP-ribose units to target proteins. This modification can have pronounced regulatory effects on target proteins. Recent studies showed that PARP-1 can poly(ADP-ribosyl)ate (PARylate) Smad proteins. However, the role of PARP-1 in the pathogenesis of systemic sclerosis (SSc) has not been investigated. METHODS: The expression of PARP-1 was determined by quantitative PCR and immunohistochemistry...
February 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29429804/clinical-outcome-of-prostate-cancer-patients-with-germline-dna-repair-mutations-retrospective-analysis-from-an-international-study
#15
Joaquin Mateo, Heather H Cheng, Himisha Beltran, David Dolling, Wen Xu, Colin C Pritchard, Helen Mossop, Pasquale Rescigno, Raquel Perez-Lopez, Verena Sailer, Michael Kolinsky, Ada Balasopoulou, Claudia Bertan, David M Nanus, Scott T Tagawa, Heather Thorne, Bruce Montgomery, Suzanne Carreira, Shahneen Sandhu, Mark A Rubin, Peter S Nelson, Johann S de Bono
BACKGROUND: Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear. OBJECTIVE: To determine whether gDDRm status impacts benefit from established therapies in mPC. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective, international, observational study. Medical records were reviewed for 390 mPC patients with known gDDRm status...
January 29, 2018: European Urology
https://www.readbyqxmd.com/read/29427345/crosstalk-of-dna-double-strand-break-repair-pathways-in-parp-inhibitor-treatment-of-brca1-2-mutated-cancer
#16
REVIEW
Shigeaki Sunada, Akira Nakanishi, Yoshio Miki
Germ-line mutations in breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) significantly increase cancer risk in hereditary breast and ovarian cancer syndrome (HBOC). Both genes function in the homologous recombination (HR) pathway of DNA double-strand break (DSB) repair process. Therefore, the DNA-repair defect characteristic in cancer cells brings therapeutic advantage for Poly(ADP-ribose) polymerase (PARP) inhibitor-induced synthetic lethality. The PARP inhibitor-based therapeutics initially causes cancer lethality but acquired resistance mechanisms have been found and need to be elucidated...
February 10, 2018: Cancer Science
https://www.readbyqxmd.com/read/29425588/saponins-isolated-from-schizocapsa-plantaginea-inhibit-human-hepatocellular-carcinoma-cell-growth-in-vivo-and-in-vitro-via-mitogen-activated-protein-kinase-signaling
#17
Yue-Wen Sun, Han-Chen Qiu, Ming-Chun Ou, Run-Li Chen, Gang Liang
The underground cane of Schizocapsa plantaginea (Hance) has long been used by Chinese ethnic minority as a constituent of anti-cancer formulae. Saponins are abundant secondary metabolic products located in the underground cane of this plant. The potential therapeutic effects of total saponins isolated from Schizocapsa plantaginea (Hance) (SSPH) on human hepatocellular carcinoma (HCC) were tested in vitro in human liver cancer cell lines, SMMC-7721 and Bel-7404. Apoptosis and cell cycle arrest were determined using flow cytometry, caspase activation was determined by ELISA, and PARP, cleaved PARP, mitogen-activated protein kinase (MAPK) expression and phosphorylation were measured using Western blotting analysis...
January 2018: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29421518/mir-7-5p-overexpression-suppresses-cell-proliferation-and-promotes-apoptosis-through-inhibiting-the-ability-of-dna-damage-repair-of-parp-1-and-brca1-in-tk6-cells-exposed-to-hydroquinone
#18
Hao Luo, Hairong Liang, Yuting Chen, Shaoyun Chen, Yongchun Xu, Longmei Xu, Jiaxian Liu, Kairu Zhou, Jucheng Peng, Guoqiang Guo, Bei Lai, Li Song, Hui Yang, Linhua Liu, Jianming Peng, Zhidong Liu, Lin Tang, Wen Chen, Huanwen Tang
Hydroquinone (HQ), one of the major metabolic products of benzene, is a carcinogen, which induces apoptosis and inhibit proliferation in lymphoma cells. microRNA-7-5p (miR-7-5p), a tumor suppressor, participates in various biological processes including cell proliferation and apoptosis regulation by repressing expression of specific oncogenic target genes. To explore whether miR-7-5p is involved in HQ-induced cell proliferation and apoptosis, we assessed the effect of miR-7-5p overexpression on induction of apoptosis analyzed by FACSCalibur flow cytometer in transfection of TK6 cells with miR-7-5p mimic (TK6- miR-7-5p)...
February 5, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29416738/parp-1-inhibitors-sensitize-hnscc-cells-to-apr-246-by-inactivation-of-thioredoxin-reductase-1-trxr1-and-promotion-of-ros-accumulation
#19
Zhi-Xian Yin, Wei Hang, Gang Liu, Yi-Shu Wang, Xiang-Feng Shen, Qian-Hui Sun, Dong-Dong Li, Yong-Ping Jian, Yang-He Zhang, Cheng-Shi Quan, Qinghua Zeng, Yu-Lin Li, Rui-Xun Zhao, Qiang Ding, Zhi-Xiang Xu
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Mutations of TP53 may reach 70% - 85% in HNSCC patients without human papillomavirus (HPV) infection. Recurrence rate remains particularly high for HNSCC patients with mutations in the TP53 gene although patients are responsive to surgery, irradiation, and chemotherapy early in the treatment. p53-Reactivation and Induction of Massive Apoptosis-1 (PRIMA-1) and its methylated analogue PRIMA-1 Met (also known as APR-246) are quinuclidine compounds that rescue the DNA-binding activity of mutant p53 (mut-p53) and restore the potential of wild-type p53...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416015/multiple-molecular-mechanisms-form-a-positive-feedback-loop-driving-amyloid-%C3%AE-42-peptide-induced-neurotoxicity-via-activation-of-the-trpm2-channel-in-hippocampal-neurons
#20
Xin Li, Lin-Hua Jiang
Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer's disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ42 activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ42-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1...
February 7, 2018: Cell Death & Disease
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