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https://www.readbyqxmd.com/read/30221935/inhibition-of-p53-murine-double-minute-2-mdm2-interactions-with-3-3-spirocyclopentene-oxindole-derivatives
#1
Maxime Gicquel, Catherine Gomez, Maria Concepcion Garcia Alvarez, Olivier Pamlard, Vincent Guérineau, Eric Jacquet, Jérôme Bignon, Arnaud Voituriez, Angela Marinetti
3,3'-spirocyclopentene oxindoles structurally related to the Wang's spiropyrrolidine oxindoles, have been highlighted as a new class of antiproliferative agents against cancer cell lines with wild-type p53 Status (IC50 up to 0.96 M on SJSA-1 and 2.9 M in HCT116 p53-wt). Inhibition of the MDM2-p53 interactions has been demonstrated through in vitro HTRF assays (IC50 up to 3.1 nM), while Western blot analysis showed activation of p53 selectively in HCT116 cancer cell lines with wild type p53.
September 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30221891/clinical-and-molecular-prognostic-factors-in-adrenocortical-carcinomas
#2
Rossella Libé
INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer, with an incidence less than 0.7-1.5 per 1 million people per year, with a poor prognosis. The overall survival (OS) depens on the ENSAT stage: in particular in metastatic ACC the OS varies between 10 and 20 months, with a 5-yrs survival around 10%. ACC present a different behaviour, probably due to a different biology. For these reason a careful prognostic classification is mandatory, in order to stratify the patients and purpose a specific management...
September 12, 2018: Minerva Endocrinologica
https://www.readbyqxmd.com/read/30221846/an-aurora-kinase-inhibitor-amg900-inhibits-glioblastoma-cell-proliferation-by-disrupting-mitotic-progression
#3
Jaewook Ryu, Jaehyuk Pyo, Chang-Woo Lee, Ja-Eun Kim
The Aurora kinase family of serine/threonine protein kinases comprises Aurora A, B, and C and plays an important role in mitotic progression. Several inhibitors of Aurora kinase have been developed as anti-cancer therapeutics. Here, we examined the effects of a pan-Aurora kinase inhibitor, AMG900, against glioblastoma cells. AMG900 inhibited proliferation of A172, U-87MG, and U-118MG glioblastoma cells by upregulating p53 and p21 and subsequently inducing cell cycle arrest and senescence. Abnormal cell cycle progression was triggered by dysregulated mitosis...
September 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/30221734/dicer-affects-cisplatin%C3%A2-mediated-apoptosis-in-epithelial-ovarian-cancer-cells
#4
Xi Wang, Hui Chen, Yiping Wen, Xiaoxin Yang, Qing Han, Ping Jiang, Zaiju Huang, Jing Cai, Zehua Wang
Dicer is an essential enzyme that processes micro (mi)-RNA precursors into mature miRNAs, and serves a critical role in cancer development and progression by regulating gene expression. However, the role of Dicer in cisplatin‑mediated apoptosis and chemotherapy resistance in epithelial ovarian cancer (EOC) cells is poorly understood. In the present study, Dicer was expressed at low levels in cisplatin‑resistant A2780 cells when compared with parental cells. In addition, knocking down Dicer using short hairpin RNA decreased the sensitivity of A2780 and CAOV3 cells to cisplatin...
September 4, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30221731/cytoprotective-effects-of-the-medicinal-herb-astragalus-membranaceus-on-lipopolysaccharide%C3%A2-exposed-cells
#5
Xian Wu, Wei Zhou, Qingshuang Wei, Peng Chen, Yan Li
Astragalus membranaceus (AM) is a traditional Chinese medicinal herb, whose cytoprotective effects remain largely unknown. Here, the bacterial endotoxin lipopolysaccharide (LPS) was applied to a human pulmonary type II‑like epithelial lung adenocarcinoma cell line, a human umbilical vein endothelial cell line, and a human bladder carcinoma cell line to construct in vitro models of intracellular oxidative stress. The authors assayed the cellular and mitochondrial cytoprotective effects of varying doses of AM root extract upon these cell lines...
September 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30221691/photothermal-therapy-with-aunrs-and-egfrmab-aunrs-inhibits-subcutaneous-transplantable-hypopharyngeal-tumors-in-nude-mice
#6
Yingying Zhang, Jiayan He, Yu Wang, Jinya Wen, Yingying Zou, Zhihong Yang, Xiaoguang He
The present study aimed to investigate the effects of photothermal therapy with gold nanorods (AuNRs) or epidermal growth factor receptor monoclonal antibody‑conjugated AuNRs (EGFRmAb‑AuNRs) on hypopharyngeal carcinoma (HC) in nude mice. In addition, the associated signaling pathways were explored. Briefly, a subcutaneous transplantable hypopharyngeal tumor model was established in nude mice injected with FaDu human HC cells. A total of 70 nude mice were randomly divided into seven groups, each of which received a different treatment...
September 12, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/30221683/aspirin-promotes-apoptosis-and-inhibits-proliferation-by-blocking-g0-g1-into-s-phase-in-rheumatoid-arthritis-fibroblast-like-synoviocytes-via-downregulation-of-jak-stat3-and-nf-%C3%AE%C2%BAb-signaling-pathway
#7
Xiaoqi Zhang, Hao Feng, Juan Du, Jing Sun, Dongfang Li, Tomoka Hasegawa, Norio Amizuka, Minqi Li
Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease. Its defining pathological characteristic is the excessive proliferation of fibroblast‑like synoviocytes (FLS), which is similar to tumor cells and results in a range of clinical problems. As a commonly used antipyretic, analgesic and anti‑inflammatory drug, aspirin is the first‑line treatment for RA. However, its mechanism of action has not been well explained. The goal is to investigate the biological effects of aspirin on primary RA‑FLS and its underlying mechanisms...
September 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30221665/protective-effects-of-taurine-against-inflammation-apoptosis-and-oxidative-stress-in-brain-injury
#8
Xiaoli Niu, Simin Zheng, Hongtao Liu, Siyuan Li
The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a non‑proteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead‑, cadmium‑, and exercise‑induced oxidative stress. Astrocytes and neuron cells were co‑cultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factor‑α, interleukin‑6, caspase‑3, p53, B‑cell lymphoma 2 and Bcl‑2‑associated X protein were determined...
September 6, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30221528/hypericin-induces-apoptosis-in-mda-mb-175-vii-cells-in-lower-dose-compared-to-mda-mb-231
#9
Niusha Abbasi Gamasaee, Maryam Radmansouri, Saeedeh Ghiasvand, Fatemeh Shahriari, Hadi Zare Marzouni, Hoda Aryan, Ehsan Jangholi, Mohammad Amin Javidi
BACKGROUND: Breast cancer is the major cause of death from cancer among women around the world. Given the drug resistance in the treatment of this disease, it is very important to identify new therapies and anticancer drugs. Many studies demonstrated that hypericin could induce apoptosis in different cancer cell lines; however, the underlying mechanism is not well understood yet. Therefore, this study aimed to evaluate the anticancer effect of hypericin in two breast cancer cell lines, one with wild type P53 and the other with mutant P53...
September 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/30220121/-significance-of-hpv-and-cell-cycle-related-proteins-in-basaloid-squamous-cell-carcinoma-of-the-larynx
#10
L F Cui, H Chang, H Y Zhao, C L Qu, Y Gao, H G Liu
Objective: To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx. Methods: Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed...
September 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/30219719/tumor-associated-carbonic-anhydrase-isoform-ix-and-xii-inhibitory-properties-of-certain-isatin-bearing-sulfonamides-endowed-with-in-vitro-antitumor-activity-towards-colon-cancer
#11
Wagdy M Eldehna, Alessio Nocentini, Sara T Al-Rashood, Ghada S Hassan, Hamad M Alkahtani, Abdulrahman A Almehizia, Ahmed M Reda, Hatem A Abdel-Aziz, Claudiu T Supuran
Three series of indolinone-based sulfonamides (3a-f, 6a-f and 9a-f) were in vitro evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the investigated sulfonamides displayed single- or double-digit nanomolar inhibitory activities towards both hCA IX (KI s: 6.2-64.8 nM) and XII (KI s: 7.1-55.6 nM) isoforms. All sulfonamides (3a-f, 6a-f and 9a-f) were in vitro examined for their potential anticancer activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines...
September 7, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/30219679/culture-filtrate-ether-extracted-metabolites-from-streptomyces-levis-abriinw111-increased-apoptosis-and-reduced-proliferation-in-acute-lymphoblastic-leukemia
#12
Behnaz Valipour, Seyede Momeneh Mohammadi, Ali Abedelahi, Behnaz Faramarzian Azimi Maragheh, Elahe Naderali, Alireza Dehnad, Hojjatollah Nozad Charoudeh
Despite the advances in the discovery of various types of anticancer drugs for curing acute lymphoblastic leukemia (ALL), their toxicity and unfavorable side effects remained as big limitations for therapeutical applications. In this regard, natural products such as Streptomyces -derived agents have shown potential applications as anticancer drugs. The present study deals with evaluating the anti-carcinogenic activity of the ether extracted metabolites derived from Streptomyces on nalm-6 and molt-4 ALL cell lines...
September 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30218854/protective-effect-of-enzymatic-hydrolysates-from-seahorse-hippocampus-abdominalis-against-h-2-o-2-mediated-human-umbilical-vein-endothelial-cell-injury
#13
Yunok Oh, Chang-Bum Ahn, Na Young Yoon, Ki Ho Nam, Yeon-Kye Kim, Jae-Young Je
Oxidative stress-mediated endothelial dysfunction and LDL oxidation have been implicated in the pathogenesis of atherosclerosis. Thus, the protection of the endothelial cells against oxidative stress-mediated injury and the inhibition of LDL oxidation by the use of antioxidants are a good strategy against atherosclerosis development. Here, we investigated the protective effect and the inhibition of LDL oxidation of seahorse H. abdominalia hydrolysates by Alcalase (SHAH). SHAH showed higher antioxidant activities by measuring DPPH, ABTS+ , and ORAC assays than the other hydrolysates...
September 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30218352/effect-of-5-aminolevulinic-acid-on-the-expression-of-carcinogenesis-related-proteins-in-cultured-primary-hepatocytes
#14
P R Menezes, C B González, A O DeSouza, D A Maria, J Onuki
Acute intermittent porphyria (AIP) is a heme pathway disorder caused by a decrease in the activity and synthesis of porphobilinogen deaminase. Thus, the first heme precursor 5-aminolevulinic acid (ALA) accumulates in the liver. Reactive oxygen species (ROS) resulting from ALA oxidation may be correlated to a higher incidence of hepatocellular carcinoma (HCC) in AIP patients. However, the molecular mechanisms of this relationship have not been thoroughly elucidated to date. In this study, we investigated the effect of increasing levels of ALA on the expression of proteins related to DNA repair, oxidative stress, apoptosis, proliferation and lipid metabolism...
September 14, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/30217928/discovery-and-characterization-of-dual-inhibitors-of-mdm2-and-nfat1-for-pancreatic-cancer-therapy
#15
Wei Wang, Jiang-Jiang Qin, Sukesh Voruganti, Bhavitavya Nijampatnam, Sadanandan E Velu, Ke-He Ruan, Ming Hu, Jianwei Zhou, Ruiwen Zhang
Overexpression and activation of the murine double minute 2 (MDM2) or nuclear factor of activated T cells 1 (NFAT1) oncoproteins frequently occur in pancreatic cancer. Most MDM2 inhibitors under development target MDM2-p53 binding and have little or no effect on cancers without functional p53, including pancreatic cancer. Some available compounds indirectly inhibit NFAT1 activity by interfering with calcineurin activity, but there are currently no specific inhibitors against NFAT1. Here we performed a high-throughput virtual and cell-based screening to yield a lead compound (MA242) that can directly bind both MDM2 and NFAT1 with high affinity, induce their protein degradation, and inhibit NFAT1-mediated transcription of MDM2 As a result of this binding, MA242 decreased cell proliferation and induced apoptosis in pancreatic cancer cell lines regardless of p53 status...
September 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/30217455/4-hydroxybenzoic-acid-4-hba-enhances-the-sensitivity-of-human-breast-cancer-cells-to-adriamycin-as-a-specific-hdac6-inhibitor-by-promoting-hipk2-p53-pathway
#16
Xu-Na Wang, Kui-Yang Wang, Xue-Song Zhang, Chao Yang, Xue-Ying Li
Breast cancer is reported a very complex disease along with heterogeneous morphological characteristics and unrelated clinical behavior, and is a leading cancer among female. Nevertheless, chemo-resistance is frequently observed. Adriamycin (ADM) is a always employed drug to treat clinical breast cancer. However, strong resistance to ADM limited its clinical efficacy. Deregulation of HDAC6 activity is linked to various diseases including cancer resulting in accumulating interest for developing HDAC6 inhibitors...
September 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30217444/aldh2-mediates-the-dose-response-protection-of-chronic-ethanol-against-endothelial-senescence-through-sirt1-p53-pathway
#17
Li Xue, Feihong Yang, Ziqi Han, Sumei Cui, Shuai Dai, Feng Xu, Chuanxin Zhang, Xuping Wang, Jiaojiao Pang, Chang Pan, Yuguo Chen
Aldehyde dehydrogenase 2 (ALDH2) plays essential roles in drinking-associated diseases or effects. As we have previously reported, ALDH2 mediates acute ethanol-induced eNOS activation in vitro. However, whether chronic ethanol treatment has a dose-response endothelial protection, as well as the possible mediating role of ALDH2 involved, is unclear. Here, we show that appropriate dose of ethanol preserved the expression and activity of ALDH2 and eNOS, and alleviated senescence-associated phenotypes in human aortic endothelial cells...
September 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30217415/in-vitro-and-in-vivo-characterization-of-a-novel-highly-potent-p53-mdm2-inhibitor
#18
Andrea Vaupel, Philipp Holzer, Stephane Ferretti, Vito Guagnano, Joerg Kallen, Robert Mah, Keiichi Masuya, Stephan Ruetz, Caroline Rynn, Achim Schlapbach, Thérèse Stachyra, Stefan Stutz, Milen Todorov, Sébastien Jeay, Pascal Furet
Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201...
August 26, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/30217020/a-new-synthetic-histone-deacetylase-inhibitor-mhy2256-induces-apoptosis-and-autophagy-cell-death-in-endometrial-cancer-cells-via-p53-acetylation
#19
Umasankar De, Ji Yeon Son, Richa Sachan, Yu Jin Park, Dongwan Kang, Kyungsil Yoon, Byung Mu Lee, In Su Kim, Hyung Ryong Moon, Hyung Sik Kim
We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide...
September 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30216985/correction-br%C3%A3-zda-v-and-coufal-j-recognition-of-local-dna-structures-by-p53-protein-int-j-mol-sci-2017-18-375
#20
Václav Brázda, Jan Coufal
The authors wish to make the following corrections to their paper [1] [...].
September 13, 2018: International Journal of Molecular Sciences
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