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https://www.readbyqxmd.com/read/28723660/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#1
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...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698396/metapristone-ru486-metabolite-suppresses-nsclc-by-targeting-egfr-mediated-pi3k-akt-pathway
#2
Jingwei Shao, Guirong Zheng, Hongning Chen, Jian Liu, Aixiao Xu, Fan Chen, Tao Li, Yusheng Lu, Jianguo Xu, Ning Zheng, Lee Jia
Therapies targeting epidermal growth factor receptor (EGFR) can effectively treat with non-small cell lung cancer (NSCLC), but NSCLC's drug resistance makes it intractable. Herein, we showed that RU486 metabolite metapristone inhibited the proliferation of various NSCLC cell lines with either wild (A549, H1299, H520) or mutated EGFR (H1975, HCC827). The suppression was resulted from inhibition by metapristone of EGFR signaling pathways through down-regulating the EGFR, PTEN, as well as AKT and ERK proteins...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28686182/a-purified-serine-protease-from-nereis-virens-and-its-impaction-of-apoptosis-on-human-lung-cancer-cells
#3
Yunping Tang, Fangmiao Yu, Guomei Zhang, Zuisu Yang, Fangfang Huang, Guofang Ding
Nereis active protease (NAP) is a novel fibrinolytic active serine protease from the polychaete Nereis virens. In this study, NAP was purified from Nereis virens and the effects of NAP on human lung cancer cells were investigated. Our results indicated that NAP inhibited the proliferation and induced apoptosis of H1299 cells in a time- and dose-dependent manner. The loss of mitochondrial membrane potential, the activation of Bax and cleaved-caspase 3/9, the release of cytochrome C, and the suppression of Bcl-2 and poly-ADP ribose polymerase were observed in NAP-treated H1299 cells by flow cytometry and Western blotting...
July 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28629998/aloe-emodin-ae-nanoparticles-suppresses-proliferation-and-induces-apoptosis-in-human-lung-squamous-carcinoma-via-ros-generation-in-vitro-and-in-vivo
#4
Yuan-Yuan Wu, Jing-Hua Zhang, Jing-Hua Gao, Yong-Sheng Li
Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28534824/isorhynchophylline-a-potent-plant-alkaloid-induces-apoptotic-and-anti-metastatic-effects-in-human-hepatocellular-carcinoma-cells-through-the-modulation-of-diverse-cell-signaling-cascades
#5
Hanwool Lee, Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#6
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28515157/carboxyamidotriazole-synergizes-with-sorafenib-to-combat-non-small-cell-lung-cancer-through-inhibition-of-nanog-and-aggravation-of-apoptosis
#7
Chen Chen, Rui Ju, Jing Shi, Wei Chen, Fangrui Sun, Lei Zhu, Juan Li, Dechang Zhang, Caiying Ye, Lei Guo
Lung cancer is the leading cause of cancer-related deaths in the world. In this study, we investigated the combination of carboxyamidotriazole (CAI) and sorafenib in NSCLC in vitro and in vivo, to test whether CAI enhances the antitumor effects of sorafenib and reduces its side effects. The combination index (CI) showed that co-administration of CAI and sorafenib synergistically inhibited the proliferation of NSCLC cells (Lewis lung carcinoma, A549, NCI-H1975). The cell death led by the treatment of combination drugs was attributed to apoptosis which was accompanied with activation of caspase 3 and poly ADP-ribose polymerase...
May 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28481901/%C3%AE-lapachone-suppresses-the-lung-metastasis-of-melanoma-via-the-mapk-signaling-pathway
#8
Ji-Ye Kee, Yo-Han Han, Dae-Seung Kim, Jeong-Geon Mun, Seong-Hwan Park, Hong-Seob So, Sung-Joo Park, Raekil Park, Jae-Young Um, Seung-Heon Hong
β-Lapachone is a natural quinone compound from Lapacho trees, which has various pharmacological effects such as anti-bacterial, anti-fungal, anti-viral, and anti-inflammatory activities. However, the effect of β-lapachone on metastasis of melanoma cells is unclear. In this study, β-lapachone reduced cell viability of metastatic melanoma cancer cell lines B16F10 and B16BL6 through induction of apoptosis via the mitogen-activated protein kinase (MAPK) pathway. Additionally, flow cytometry results showed that β-lapachone increased DNA content in the G0/G1 phase of the cell cycle...
2017: PloS One
https://www.readbyqxmd.com/read/28459519/diterpenoid-tanshinones-the-extract-from-danshen-radix-salviae-miltiorrhizae-induced-apoptosis-in-nine-human-cancer-cell-lines
#9
Li Shen, Zhaohuan Lou, Guangshun Zhang, Guanhua Xu, Guangji Zhang
OBJECTIVE: To identify the active anti-tumor constituents in the extract from Danshen (Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions. METHODS: First, we introduced a two-step counter- current chromatography to extract the therapeutically active diterpenoid, tanshinone from Danshen (Radix Salviae Miltiorrhizae). The cholecystokinin (CCK-8) method was used to evaluate the inhibitory effect of diterpenoid tanshinone in liver cancer QGY-7703, lung cancer PC9, lung cancer A549, gastric cancer MKN-45, gastric cancer HGC-27, colon cancer HCT116, myeloma cellU266/ RPMI8226, and human breast cancer MCF-7 in vitro...
August 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
https://www.readbyqxmd.com/read/28454429/polyphenolic-compounds-from-korean-lonicera-japonica-thunb-induces-apoptosis-via-akt-and-caspase-cascade-activation-in-a549-cells
#10
Kwang Il Park, Hyeonsoo Park, Arulkumar Nagappan, Gyeong Eun Hong, Silvia Yumnam, Ho Jeong Lee, Eun Hee Kim, Won Sup Lee, Sung Chul Shin, Jin A Kim, Sang Joon Lee, Jin Yeul Ma, Taesun Min, Jeong Doo Heo, Gon Sup Kim
Lonicera japonica Thunb. (L. japonica T.) has historically been used in Korean herbal medicine due to its anticancer and protective effects on the respiratory system. In the present study, the polyphenolic compounds in L. japonica T. were investigated using high-performance liquid chromatography coupled with tandem mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a dose-dependent manner. Flow cytometry and western blot analysis demonstrated that polyphenolic compounds induce apoptosis by regulating the protein expression levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2-associated X-protein/B-cell lymphoma-extra large ratio...
April 2017: Oncology Letters
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
#11
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
#12
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...
April 18, 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
#13
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
#14
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
#15
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
#16
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...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28242752/phase-i-dose-escalation-two-part-trial-of-the-parp-inhibitor-talazoparib-in-patients-with-advanced-germline-brca1-2-mutations-and-selected-sporadic-cancers
#17
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 PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, 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%)...
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28195671/trachycladines-and-analogues-synthesis-and-evaluation-of-anticancer-activity
#18
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
#19
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
#20
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
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