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https://www.readbyqxmd.com/read/28425856/apicidin-inhibited-proliferation-and-invasion-and-induced-apoptosis-via-mitochondrial-pathway-in-non-small-cell-lung-cancer-glc-82-cells
#1
Jianye Zhang, Zhenzhu Lai, Wenjing Huang, Huiping Ling, Minting Lin, Sili Tang, Yun Liu, Yiwen Tao
Apicidin, an inhibitor of histone deacetylase obtained from the mangrove endophytic fungi Fusarium sp., showed a wide range of antiproliferative activity against various cancer cell lines. Apicidin has also been reported to induce apotosis via Fas/Fas ligand. Yet few studies have focused on mitochondrial pathway for its anti-tumor activity. Here, we evaluated its involved mitochondrial mechanism against lung cancer GLC-82 cells. Its structure was elucidated by MS and NMR spectroscopic data, and comparison of those data with published data...
April 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28412751/poly-adp-ribose-polymerase-inhibitor-an-effective-radiosensitizer-in-lung-and-pancreatic-cancers
#2
Kedar Hastak, Steven Bhutra, Renate Parry, James M Ford
The development of stereotactic body radiation therapy (SBRT) has revolutionized radiation therapy for lung cancers and is an emerging treatment option for pancreatic cancers. However, there are many questions on how to optimize its use in chemoradiotherapy. The most relevant addition to radiotherapy regimens are inhibitors of DNA repair and DNA damage response pathways. One such class of agents are inhibitors of poly (ADP-ribose) polymerase (PARP). In this study we examined the effects of the PARP inhibitor LT626 in combination with ionizing radiation in lung and pancreatic cancers...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394654/inhibiting-igf-1r-attenuates-cell-proliferation-and-vegf-production-in-igf-1r-over-expressing-egfr-mutant-non-small-cell-lung-cancer-cells
#3
Chang Dong Yeo, Young Ae Kim, Hwa Young Lee, Jin Woo Kim, Sang Haak Lee, Seung Joon Kim, Soon Seog Kwon, Yong Hyun Kim, Seok Chan Kim
PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot...
February 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28351307/coptisine-induced-cell-cycle-arrest-at-g2-m-phase-and-reactive-oxygen-species-dependent-mitochondria-mediated-apoptosis-in-non-small-cell-lung-cancer-a549-cells
#4
Poorna Chandra Rao, Sajeli Begum, Mahendra Sahai, D Saketh Sriram
This study aimed to explore the effect of coptisine on non-small-cell lung cancer and its mechanism through various in vitro cellular models (A549). Results claimed significant inhibition of proliferation by coptisine against A549, H460, and H2170 cells with IC50 values of 18.09, 29.50, and 21.60 µM, respectively. Also, coptisine exhibited upregulation of pH2AX, cell cycle arrest at G2/M phase, and downregulation of the expression of cyclin B1, cdc2, and cdc25C and upregulation of p21 dose dependently. Furthermore, induction of apoptosis in A549 cells by coptisine was characterized by the activation of caspase 9, caspase 8, and caspase 3, and cleavage of poly adenosine diphosphate ribose polymerase...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#5
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28262615/dehydrobruceine-b-enhances-the-cisplatin-induced-cytotoxicity-through-regulation-of-the-mitochondrial-apoptotic-pathway-in-lung-cancer-a549-cells
#6
Zhuqing Huang, Guotao Yang, Tao Shen, Xiaoning Wang, Haizhen Li, Dongmei Ren
Dehydrobruceine B (DHB) is a quassinoid isolated from Brucea javanica. We have shown previously that DHB induced apoptosis on two kinds of lung cancer cell lines, A549 and NCI-H292. In the present study, we investigated the interactions of DHB and cisplatin (CDDP) on apoptotic-related cancer cell death. Synergistic effects on cell proliferation and apoptosis were observed when A549 cells were treated with DHB plus CDDP. DHB combined CDDP exposure increased depolarization of mitochondrial membrane potential (MMP) and release of cytochrome c from mitochondria into the cytoplasm...
March 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28242752/phase-i-dose-escalation-2-part-trial-of-poly-adp-ribose-polymerase-inhibitor-talazoparib-in-patients-with-advanced-germline-brca1-2-mutations-and-selected-sporadic-cancers
#7
Johann de Bono, Ramesh K Ramanathan, Lida Mina, Rashmi Chugh, John Glaspy, Saeed Rafii, Stan Kaye, Jasgit Sachdev, John Heymach, David C Smith, Joshua W Henshaw, Ashleigh Herriott, Miranda Patterson, Nicola J Curtin, Lauren Averett Byers, Zev A Wainberg
Talazoparib inhibits poly(ADP-ribose) polymerase (PARP) catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this 2-part, phase I, first-in-human trial. Antitumor activity, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%)...
February 27, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28195671/trachycladines-and-analogues-synthesis-and-evaluation-of-anticancer-activity
#8
Zisis V Peitsinis, Achilleas G Mitrakas, Eirini A Nakiou, Dafni A Melidou, Dimitra Kalamida, Christos Kakouratos, Michael I Koukourakis, Alexandros E Koumbis
The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a d-ribose-derived chiron. Naturally occurring trachycladines A and B and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung, and cervical cancer). Parent trachycladine A and two analogues (the diacetate of the 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) resulted in a significant decrease in cell viability, with the latter exhibiting a stronger effect...
February 14, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28182994/atm-deficient-colorectal-cancer-cells-are-sensitive-to-the-parp-inhibitor-olaparib
#9
Chen Wang, Nicholas Jette, Daniel Moussienko, D Gwyn Bebb, Susan P Lees-Miller
The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors...
April 2017: Translational Oncology
https://www.readbyqxmd.com/read/28177129/role-of-parp-activity-in-lung-cancer-induced-cachexia-effects-on-muscle-oxidative-stress-proteolysis-anabolic-markers-and-phenotype
#10
Alba Chacon-Cabrera, Mercè Mateu-Jimenez, Klaus Langohr, Clara Fermoselle, Elena García-Arumí, Antoni L Andreu, Jose Yelamos, Esther Barreiro
Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1(-/-) ) and Parp-2(-/-) mice...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28146604/the-clinically-used-poly-adp-ribose-polymerase-parp-inhibitor-olaparib-improves-organ-function-suppresses-inflammatory-responses-and-accelerates-wound-healing-in-a-murine-model-of-third-degree-burn-injury
#11
Akbar Ahmad, Gabor Olah, David N Herndon, Csaba Szabo
BACKGROUND AND PURPOSE: The PARP inhibitor olaparib has recently been approved for human use for the therapy of cancer. Considering the role of PARP in critical illness, we tested the effect of olaparib in a murine model of burn injury, in order to begin exploring the feasibility of repurposing olaparib for the therapy of burn patients. EXPERIMENTAL APPROACH: Mice were subjected to scald burn injury and randomized into vehicle or olaparib (10 mg/kg/day i.p.) groups...
February 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28119809/euphorbia-factor-l2-induces-apoptosis-in-a549-cells-through-the-mitochondrial-pathway
#12
Minting Lin, Sili Tang, Chao Zhang, Hubiao Chen, Wenjing Huang, Yun Liu, Jianye Zhang
Euphorbia factor L2, a lathyrane diterpenoid isolated from caper euphorbia seed (the seeds of Euphorbia lathyris L.), has been traditionally applied to treat cancer. This article focuses on the cytotoxic activity of Euphorbia factor L2 against lung carcinoma A549 cells and the mechanism by which apoptosis is induced. We analyzed the cytotoxicity and related mechanism of Euphorbia factor L2 with an MTT assay, an annexin V-FITC/PI test, a colorimetric assay, and immunoblotting. Euphorbia factor L2 showed potent cytotoxicity to A549 cells...
January 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28117012/current-status-and-perspectives-regarding-the-therapeutic-potential-of-targeting-egfr-pathway-by-curcumin-in-lung-cancer
#13
Mojtaba Shafiee, Elham Mohamadzade, Soudabeh ShahidSales, Samaneh Khakpouri, Mina Maftouh, Seyed Alireza Parizadeh, Seyed Mahdi Hasanian, Amir Avan
Lung cancer is among the leading cause of cancer-related-deaths and non-small cell lung cancer (NSCLC) is the most common form of lung cancer. More than 70% of NSCLC patients have locally advanced or metastatic disease at diagnosis, which are then being treated with platinum-based chemotherapy or epidermal-growth-factor-receptor (EGFR) inhibitors in patients harboring activating EGFR-mutations. Several molecules which target multiple ErbB receptors and EGFR, have been developed, including gefitinib and erlotinib, although most of the patients become resistance...
January 23, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28081275/role-of-xrcc1-gene-polymorphisms-in-non-small-cell-lung-cancer-cisplatin-based-chemotherapy-and-their-effect-on-clinical-and-pathological-characteristics
#14
H F Liu, J S Liu, J H Deng, R R Wu
Non-small cell lung cancer (NSCLC) is the most common cancer globally. The XRCC1 protein interacts with ligase and poly(ADP-ribose) polymerase to repair cisplatin-induced DNA damage. The authors of previous studies have reported XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms and advanced NSCLC prognosis, but the results are inconclusive. We investigated the association between clinical outcome and XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms in advanced NSCLC patients treated with cisplatin...
December 23, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28058814/overexpression-of-tnks1bp1-in-lung-cancers-and-its-involvement-in-homologous-recombination-pathway-of-dna-double-strand-breaks
#15
Wei Tan, Hua Guan, Lian-Hong Zou, Yu Wang, Xiao-Dan Liu, Wei-Qing Rang, Ping-Kun Zhou, Hua-Dong Pei, Cai-Gao Zhong
TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation...
February 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28008145/msh2-brca1-expression-as-a-dna-repair-signature-predicting-survival-in-early-stage-lung-cancer-patients-from-the-ifct-0002-phase-3-trial
#16
Guénaëlle Levallet, Fatéméh Dubois, Pierre Fouret, Martine Antoine, Solenn Brosseau, Emmanuel Bergot, Michèle Beau-Faller, Valérie Gounant, Elisabeth Brambilla, Didier Debieuvre, Olivier Molinier, Françoise Galateau-Sallé, Julien Mazieres, Elisabeth Quoix, Jean-Louis Pujol, Denis Moro-Sibilot, Alexandra Langlais, Franck Morin, Virginie Westeel, Gérard Zalcman
INTRODUCTION: DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. METHODS: We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002)...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27960087/leveraging-an-nqo1-bioactivatable-drug-for-tumor-selective-use-of-poly-adp-ribose-polymerase-inhibitors
#17
Xiumei Huang, Edward A Motea, Zachary R Moore, Jun Yao, Ying Dong, Gaurab Chakrabarti, Jessica A Kilgore, Molly A Silvers, Praveen L Patidar, Agnieszka Cholka, Farjana Fattah, Yoonjeong Cha, Glenda G Anderson, Rebecca Kusko, Michael Peyton, Jingsheng Yan, Xian-Jin Xie, Venetia Sarode, Noelle S Williams, John D Minna, Muhammad Beg, David E Gerber, Erik A Bey, David A Boothman
Therapeutic drugs that block DNA repair, including poly(ADP-ribose) polymerase (PARP) inhibitors, fail due to lack of tumor-selectivity. When PARP inhibitors and β-lapachone are combined, synergistic antitumor activity results from sustained NAD(P)H levels that refuel NQO1-dependent futile redox drug recycling. Significant oxygen-consumption-rate/reactive oxygen species cause dramatic DNA lesion increases that are not repaired due to PARP inhibition. In NQO1(+) cancers, such as non-small-cell lung, pancreatic, and breast cancers, cell death mechanism switches from PARP1 hyperactivation-mediated programmed necrosis with β-lapachone monotherapy to synergistic tumor-selective, caspase-dependent apoptosis with PARP inhibitors and β-lapachone...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27923905/%C3%AE-lapachone-inhibits-lung-metastasis-of-colorectal-cancer-by-inducing-apoptosis-of-ct26-cells
#18
Ji-Ye Kee, Yo-Han Han, Jinbong Park, Dae-Seung Kim, Jeong-Geon Mun, Kwang Seok Ahn, Hyun-Jung Kim, Jae-Young Um, Seung-Heon Hong
BACKGROUND: β-Lapachone is a quinone-containing compound found in red lapacho (Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. METHODS: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38)...
December 5, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27919953/bishydroquinone-renieramycin-m-induces-apoptosis-of-human-lung-cancer-cells-through-a-mitochondria-dependent-pathway
#19
Tatchakorn Pinkhien, Arnatchai Maiuthed, Supakarn Chamni, Khanit Suwanborirux, Naoki Saito, Pithi Chanvorachote
BACKGROUND: Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells. METHODS: HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27898232/unfolded-protein-response-promotes-doxorubicin-induced-nonsmall-cell-lung-cancer-cells-apoptosis-via-the-mtor-pathway-inhibition
#20
Xiaofang Zhao, Yan Yang, Fuli Yao, Bin Xiao, Ying Cheng, Chunhong Feng, Chunyan Duan, Chunyan Zhang, Youping Liu, Hong Li, Bo Xiao, Rongyang Dai
Drug resistance is extremely common in nonsmall cell lung cancer (NSCLC) and is one of the major problems in NSCLC chemotherapy. However, the detailed mechanisms remain largely unknown. Unfolded protein response (UPR) is involved in the tumorigenesis of NSCLC. Here, the authors demonstrated that the UPR promotes poly (ADP-ribose) polymerase activation (PARP) cleavage in NSCLC cells on doxorubicin treatment, which is a hallmark of apoptosis and caspase activation. In NSCLC cells, doxorubicin treatment triggers the UPR activation, which subsequently promotes doxorubicin-mediated apoptosis...
December 2016: Cancer Biotherapy & Radiopharmaceuticals
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