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caspase 8

Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Sinéad Kinsella, Jochen H M Prehn
In this issue of Molecular Cell, Fu et al. (2016) present a detailed structural analysis of death-inducing signaling complex (DISC) assembly and regulation through flexible caspase-8 interactions with cFLIPL, cFLIPS, and the viral inhibitor MC159, thereby identifying novel apoptosis control mechanisms.
October 20, 2016: Molecular Cell
Chihua Wu, Jing Luo
BACKGROUND Long non-coding RNA (lncRNA) UCA1 is an oncogene in breast cancer. The purpose of this study was to investigate the role of UCA1 in tamoxifen resistance of estrogen receptor positive breast cancer cells. MATERIAL AND METHODS Tamoxifen sensitive MCF-7 cells were transfected for UCA1 overexpression, while tamoxifen resistant LCC2 and LCC9 cells were transfected with UCA siRNA for UCA1 knockdown. qRT-PCR was performed to analyze UCA1 expression. CCK-8 assay, immunofluorescence staining of cleaved caspase-9, and flow cytometric analysis of Annexin V/PI staining were used to assess tamoxifen sensitivity...
October 21, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yong Fang, Zi Xu, Yi Shi, Fei Pei, Wenjian Yang, Ning Ma, Benard Muinde Kimatu, Kunlun Liu, Weifen Qiu, Qiuhui Hu
This study aimed to investigate the protection mechanism of Se-containing protein hydrolysates (SPH) from Se-enriched rice on Pb(2+)-induced apoptosis in PC12 and RAW264.7 cells. Results showed that SPHs could alleviate Pb(2+)-induced morphological changes of apoptosis and the loss of mitochondrial transmembrane potential in both cell types. Besides this, SPHs could significantly reduce the activation of caspase-3, -8, -9 induced by Pb(2+), reverse the Pb(2+)-induced upregulation of Bax and release of cytochrome C, and downregulate Bcl-2 in cells...
March 15, 2017: Food Chemistry
Yang Li, Jian Li, Zhiwen Hou, Yang Yu, Bo Yu
The primary physiological function of Krüppel-like zinc-finger transcription factor (KLF5) is the regulation of cardiovascular remodeling. Vascular remodeling is closely related to the amelioration of various ischemic diseases. However, the underlying correlation of KLF5 and ischemia is not clear. In this study, we aim to investigate the role of KLF5 in myocardial ischemia reperfusion (IR) injury and the potential mechanisms involved. Cultured H9C2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/Rep) to mimic myocardial IR injury in vivo...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Al-Abboodi Shakir Ashwaq, Mothanna Sadiq Al-Qubaisi, Abdullah Rasedee, Ahmad Bustamam Abdul, Yun Hin Taufiq-Yap, Swee Keong Yeap
Dentatin (DEN), purified from the roots of Clausena excavata Burm f., has poor aqueous solubility that reduces its therapeutic application. The aim of this study was to assess the effects of DEN-HPβCD (hydroxypropyl-β-cyclodextrin) complex as an anticancer agent in HT29 cancer cell line and compare with a crystal DEN in dimethyl sulfoxide (DMSO). The exposure of the cancer cells to DEN or DEN-HPβCD complex leads to cell growth inhibition as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay...
October 18, 2016: International Journal of Molecular Sciences
Xiaoye Liu, Shuangyang Ding, Peijie Shi, Richard Dietrich, Erwin Märtlbauer, Kui Zhu
Bacillus cereus is an opportunistic pathogen that often causes foodborne infectious diseases and food poisoning. Non-haemolytic enterotoxin (Nhe) is the major toxin found in almost all enteropathogenic B. cereus and B. thuringiensis isolates. However, little is known about the cellular response after Nhe triggered pore formation on cell membrane. Here we demonstrate that Nhe induced cell cycle arrest at G0 /G1 phase and provoked apoptosis in Vero cells, most likely associated with mitogen-activated protein kinase (MAPK) and death receptor pathways...
October 20, 2016: Cellular Microbiology
Marie Jazzara, Ahmed Ghannam, Chadi Soukkarieh, Hossam Murad
BACKGROUND: Sulfated Polysaccharides (SPs) possess spectrum of pharmacological and therapeutic properties that could attributed to their origins variation, chemical structures and biological activities. Various studies have shown the impact of SPs on proliferation in different cancer cell lines. OBJECTIVES: In this study, we have evaluated the biological effects of λ-carrageenan, a highly SP, extracted from the red seaweed Laurencia papillosa, on MDA-MB-231 cancer cell line...
August 2016: Iranian Journal of Cancer Prevention
Yong-Chao Ma, Zhi-Xin Wang, Shao-Ju Jin, Yan-Xin Zhang, Guo-Qiang Hu, Dong-Tao Cui, Jiang-Shuan Wang, Min Wang, Fu-Qing Wang, Zhi-Jun Zhao
Both tyrosine kinase and topoisomerase II (TopII) are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
2016: PloS One
S D Wang, Z H Wang, H Q Yan, M Y Ren, S Q Gao, G Q Zhang
BACKGROUND: Zerumbone (ZER) is a phytochemical that appears to regulate cell proliferation and apoptosis. It has been reported to have an anti-tumour effect in various malignant cells; however, the effect and the mechanism of ZER on melanoma cells needs to be clarified. AIM: To explore whether ZER has an effect on human melanoma cells and to identify the mechanisms involved. METHODS: We determined the chemotherapeutic action of ZER on the human malignant melanoma (MM) A375 cell line by CCK-8 immunohistochemistry, Hoechst 33342 staining and flow cytometry analysis...
October 19, 2016: Clinical and Experimental Dermatology
Manish Kumar Pal, Shyama Pyari Jaiswar, Ajeet Kumar Srivastav, Shruti Goyal, Ashish Dwivedi, Ankit Verma, Jyoti Singh, Anumesh Kumar Pathak, Pushpa Lata Sankhwar, Ratan Singh Ray
Ovarian cancer is fourth most common and lethal among all gynecologic malignancies. The chemotherapy usually requires in all stages of ovarian cancer but drugs have several side effects. We hypothesized that use of combination therapy of paclitaxel (PTX) and phytochemical piperine (PIP) may reduce the PTX dose as well as toxicity.The human ovarian adenocarcinomas SKOV3 cell treated with PTX-5nM and PIP-10µM after determination of IC50 by MTT assay. Reactive oxygen species generation, mitochondrial membrane potential (MMP), DNA damage, cell death pathway markers as release of cyt-c, Bax/Bcl2-caspase-3 and cell cycle arrest were analyzed...
October 15, 2016: European Journal of Pharmacology
K Bridget Brosnihan, Victor M Pulgar, Manish S Bharadwaj, Liomar A A Neves, Liliya M Yamaleyeva
BACKGROUND: Cyclooxygenase (COX)-derived prostanoids (PGE2, PGI2) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy...
October 18, 2016: Reproductive Biology and Endocrinology: RB&E
Rashi Arora, Sharad Sawney, Vikas Saini, Chris Steffi, Manisha Tiwari, Daman Saluja
BACKGROUND: A handful of studies have exploited antitumor potential of esculetin, a dihydroxy coumarine derivative; the targets to which it binds and the possible downstream mechanism for its cytotoxicity in cancer cells remain to be elucidated. Using pancreatic cancer cell lines as a model system, herein the study was initiated to check the efficacy of esculetin in inhibiting growth of these cancer cells, to decipher mechanism of its action and to predict its direct binding target protein...
October 18, 2016: Molecular Cancer
Hugues Kamdem Paumo, Tshepiso Jan Makhafola, Malose Jack Mphahlele
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon-carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells...
October 14, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nobuhiro Nagai, Satoru Iwata, Hirokazu Kaji, Kaori Sampei, Yuki Katsukura, Hideyuki Onami, Matsuhiko Nishizawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe
It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices...
November 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
C-Y Lin, T-W Chang, W-H Hsieh, M-C Hung, I-H Lin, S-C Lai, Y-J Tzeng
Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1...
2016: Cell Death Discovery
Encheng Yang, Xiao Li, Ningyi Jin
AIM: This study was aimed to evaluate the therapeutic efficiency of a non-virus based specific chimeric multi-domain DNA transferred with apoptin in human hepatocellular carcinoma (HCC) HepG-2 cells in vitro and in mice H22 cells in vivo. METHODS: We firstly constructed the multi-domain recombinant chimeric proteins based on recombinant proteins [G (yeast GAL4), NG (none GAL4), TG (GAL4 + Tat protein) and TNG (Tat protein)] and pUAS-Apoptin plasmid, and transfected them into human HepG-2 cells...
2016: Cancer Cell International
Jun-Wei Shen, Ming Shan, Yuan-Yuan Peng, Ting-Jun Fan
PURPOSE: To investigate the cytotoxic effect of latanoprost on corneal stroma and its underlying cellular and molecular mechanisms using non-transfected human corneal stromal (HCS) cells as an in vitro model. METHODS: After HCS cells were treated with latanoprost at concentrations varying from 50 mg/l (clinical therapeutic dosage) to 0.78125 mg/l, and cell morphology, cell viability, and cell cycle were detected by light microscopy, methyl thiazolyl tetrazolium assay, and flow cytometry (FCM) with propidium iodide (PI) staining, respectively...
October 17, 2016: Current Eye Research
Zena Huang, Xiaobian Dong, Xiaodong Zhuang, Xun Hu, Lichun Wang, Xinxue Liao
Hyperglycemia serves an important role in the pathogenesis of diabetic cardiomyopathy. The aim of the present study was to investigate whether exogenous hydrogen sulfide (H2S) protects against high glucose‑induced inflammation and cytotoxicity in cardiac cells by inhibiting the p38 mitogen‑activated protein kinase (MAPK)/nuclear factor‑κB (NF‑κB), cyclooxygenase‑2 (COX‑2) and inducible nitric oxide synthase (iNOS) signaling pathways. Rat H9c2 myocardium cells were exposed to 33 mM glucose (high glucose, HG) for 24 h to stimulate HG‑induced cytotoxicity...
October 13, 2016: Molecular Medicine Reports
Yali Chen, Qianxiang Zhou, Lei Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Increasing resistance of imatinib, a BCR-ABL tyrosine kinase inhibitor, hinders its use in the therapy of chronic myeloid leukemia (CML). The PI3K pathway is known to be closely involved in BCR-ABL transformation and the tumorigenesis of CML, suggesting that PI3K may be a potential target for CML therapy. Idelalisib, a specific inhibitor of PI3K p110δ, has been approved for the treatment of chronic lymphocytic leukemia (CLL). However, the antileukemia effect of idelalisib on CML remains unknown. In the present study, the antileukemia activity of idelalisib alone or in combination with imatinib was investigated by use of K562 cells...
October 17, 2016: Oncology Reports
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