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https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#1
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423654/mcl-1-regulates-reactive-oxygen-species-via-nox4-during-chemotherapy-induced-senescence
#2
Abeba Demelash, Lukas W Pfannenstiel, Li Liu, Brian R Gastman
Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423593/anti-cancer-effect-of-novel-pak1-inhibitor-via-induction-of-puma-mediated-cell-death-and-p21-mediated-cell-cycle-arrest
#3
Tae-Gyun Woo, Min-Ho Yoon, Shin-Deok Hong, Jiyun Choi, Nam-Chul Ha, Hokeun Sun, Bum-Joon Park
Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419994/degradation-of-mcl-1-through-gsk-3%C3%AE-activation-regulates-apoptosis-induced-by-bufalin-in-non-small-cell-lung-cancer-h1975-cells
#4
Xiao-Hong Kang, Jing-Hang Zhang, Qing-Qin Zhang, Yan-Hui Cui, Ying Wang, Wei-Zheng Kou, Zhan-Hui Miao, Ping Lu, Li-Fang Wang, Zhen-Ye Xu, Fei Cao
BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting...
April 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28415755/mitochondrial-matrix-chaperone-and-c-myc-inhibition-causes-enhanced-lethality-in-glioblastoma
#5
Chiaki Tsuge Ishida, Chang Shu, Marc-Eric Halatsch, Mike-Andrew Westhoff, Dario C Altieri, Georg Karpel-Massler, Markus David Siegelin
Malignant gliomas display high levels of the transcription factor c-myc and organize a tumor specific chaperone network within mitochondria. Here, we show that c-myc along with mitochondrial chaperone inhibition displays massive tumor cell death. Inhibition of mitochondrial matrix chaperones and c-myc was established by utilizing genetic as well as pharmacological approaches. Bromodomain and extraterminal (BET) family protein inhibitors, JQ1 and OTX015, were used for c-myc inhibition. Gamitrinib was applied to interfere with mitochondrial matrix chaperones...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415572/inhibition-of-iron-overload-induced-apoptosis-and-necrosis-of-bone-marrow-mesenchymal-stem-cells-by-melatonin
#6
Fan Yang, Yuan Li, Gege Yan, Tianyi Liu, Chao Feng, Rui Gong, Ye Yuan, Fengzhi Ding, Lai Zhang, Elina Idiiatullina, Valentin Pavlov, Zhenbo Han, Wenya Ma, Qi Huang, Ying Yu, Zhengyi Bao, Xiuxiu Wang, Bingjie Hua, Zhimin Du, Benzhi Cai, Lei Yang
Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls' Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner...
March 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412247/activation-of-phospholipase-c-%C3%AE-1-and-translocation-of-phosphatidylinositol-3-4-5-trisphosphate-3-phosphatase-contribute-to-gl-v9-induced-apoptosis-in-human-gastric-cancer-cells
#7
Kai Zhao, Guojun Li, Yuyuan Yao, Yuxin Zhou, Zhiyu Li, Qinglong Guo, Na Lu
Gastric cancer is the most common type of tumor in developing countries and the fourth most frequently diagnosed cancer worldwide. Here, we demonstrated the apoptotic effects of GL-V9 on several human gastric cancer cells and selected MGC-803 cells to uncover the underlying mechanism. GL-V9 elevated Bax/Bcl-2 ratio, abated mitochondrial membrane potential and triggered the onset of apoptotic execution in MGC-803 cells. Our research revealed that CHOP silencing could not inhibit apoptosis, neither could it block Ca(2+) release, suggesting that GL-V9-induced apoptosis was independent of CHOP...
April 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28410239/homoharringtonine-suppresses-imatinib-resistance-via-the-bcl-6-p53-pathway-in-chronic-myeloid-leukemia-cell-lines
#8
Qian Wang, Wei Ding, Yihan Ding, Jingjing Ma, Zhaoye Qian, Jingxian Shao, Yufeng Li
BACKGROUND: The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo. RESULTS: Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404630/mir-424-322-503-is-a-breast-cancer-tumor-suppressor-whose-loss-promotes-resistance-to-chemotherapy
#9
Ruth Rodriguez-Barrueco, Erin A Nekritz, François Bertucci, Jiyang Yu, Felix Sanchez-Garcia, Tizita Z Zeleke, Andrej Gorbatenko, Daniel Birnbaum, Elena Ezhkova, Carlos Cordon-Cardo, Pascal Finetti, David Llobet-Navas, Jose M Silva
The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28401933/bcl-xl-mediates-ripk3-dependent-necrosis-in-m-tuberculosis-infected-macrophages
#10
X Zhao, N Khan, H Gan, F Tzelepis, T Nishimura, S-Y Park, M Divangahi, H G Remold
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28395566/wt1-protein-is-cleaved-by-caspase-3-in-apoptotic-leukemic-cells
#11
Jichen Ruan, Shenmeng Gao, Junjun Yang, Haiying Li, He Huang, Xiaoqun Zheng
The aberrant overexpression of Wilms' tumor-1 gene (WT1) plays an important role in blast cell survival and resistance to chemotherapy in acute myeloid leukemia (AML). Here, we found in chemotherapeutic drug etoposide-induced apoptosis, WT1 protein was cleaved into smaller fragment by caspase-3 in leukemic cells. The cleavage was blocked by pan-caspase inhibitor and special caspase-3 inhibitor, suggesting that caspase-3 might cleave WT1 protein. Furthermore, recombinant active caspase-3 cleaved the Flag-WT1 and GST-WT1 proteins in vitro...
April 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28389245/thymol-inhibits-bladder-cancer-cell-proliferation-via-inducing-cell-cycle-arrest-and-apoptosis
#12
Yi Li, Jia-Ming Wen, Chuan-Jun Du, Su-Min Hu, Jia-Xi Chen, Shi-Geng Zhang, Nan Zhang, Feng Gao, Shao-Jiang Li, Xia-Wa Mao, Hiroshi Miyamoto, Ke-Feng Ding
Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins...
April 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28386348/inhibition-of-cox-2-pge2-cascade-ameliorates-cisplatin-induced-mesangial-cell-apoptosis
#13
Xiaowen Yu, Yunwen Yang, Hui Yuan, Meng Wu, Shuzhen Li, Wei Gong, Jing Yu, Weiwei Xia, Yue Zhang, Guixia Ding, Songming Huang, Zhanjun Jia, Aihua Zhang
Cisplatin is one of the most potent cytotoxic drug for the treatment of many types of cancer. However, the side effects on normal tissues, particularly on the kidney, greatly limited its use in clinic. Emerging evidence demonstrated that cisplatin could directly cause mesangial cell apoptosis, while the potential mechanism is still elusive. Here we examined the contribution of COX-2 in cisplatin-induced mesangial cell apoptosis. Firstly, we found cisplatin induced cell apoptosis in mesangial cells shown by increased number of apoptotic cells in parallel with the upregulation of Bax and the downregulation of Bcl-2...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386203/intervention-action-of-total-flavonoids-from-root-of-ilex-pubescens-in-cerebral-ischemic-tolerance-with-blood-stasis
#14
Mingsan Miao, Lihua Cao, Kun Xu, Weiyun Xin, Yan Zheng
The aim of this study was to explore the action characters of total flavonoids from MDQ on cerebral ischemic tolerance with blood stasis. Fully understanding the mechanism of action of total flavonoids from MDQ is helpful for the development of new drugs and the utilization of resources. Male Wistar rat model of blood stasis was established by injecting dexamethasone into the intramuscular side of the thigh. Then they were given related drugs via an intragastric administration for a successive 10 days. After 7 days, the following occurred: firstly, the method of blocking the bilateral common carotid artery (CCA) was used for 10 min, followed by a restoration of perfusion...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28378125/humanin-inhibits-apoptosis-in-pituitary-tumor-cells-through-several-signaling-pathways-including-nf-%C3%AE%C2%BAb-activation
#15
María Florencia Gottardo, Mariela Moreno Ayala, Jimena Ferraris, Sandra Zárate, Daniel Pisera, Marianela Candolfi, Gabriela Jaita, Adriana Seilicovich
Humanin (HN) and Rattin (HNr), its homologous in the rat, are peptides with cytoprotective action in several cell types such as neurons, lymphocytes and testicular germ cells. Previously, we have shown that HNr is expressed in pituitary cells and that HN inhibited the apoptotic effect of TNF-α in both normal and tumor pituitary cells. The aim of the present study was to identify signaling pathways that mediate the antiapoptotic effect of HN in anterior pituitary cells from ovariectomized rats and in GH3 cells, a somatolactotrope cell line...
April 4, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28376129/lrg1-promotes-proliferation-and-inhibits-apoptosis-in-colorectal-cancer-cells-via-runx1-activation
#16
Ying Zhou, Xintian Zhang, Jingjing Zhang, Jingyuan Fang, Zhizheng Ge, Xiaobo Li
Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been shown to be involved in various human malignancies. Whether it plays a role in colorectal cancer (CRC) development remains unclear. Here, we investigated whether and through what mechanism LRG1 functions in human CRC cells. The plasma level of LRG1 was significantly increased in CRC patients, but it was remarkably decreased in patients with resected colorectal cancers. Meanwhile, both mRNA and protein levels of LRG1 were remarkable overexpressed in CRC tissues than normal tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28374135/oxabicycloheptene-sulfonate-protects-against-%C3%AE-amyloid-induced-toxicity-by-activation-of-pi3k-akt-and-erk-signaling-pathways-via-gper1-in-c6-cells
#17
Li-Juan Deng, Chen Cheng, Jun Wu, Cai-Hua Wang, Hai-Bing Zhou, Jian Huang
Oxabicycloheptene sulfonate (OBHS) is a novel bicyclic core selective estrogen receptor modulator (SERM) with estrogen receptor (ER) antagonistic-activity and anti-inflammatory activity. However, little is known about protective action of OBHS on neurodegenerative disorders. In the present study, OBHS demonstrated a remarkably protective effect against amyloid beta (Aβ) induced cytotoxicity via G-protein-coupled estrogen receptor 1 (GPER1) in rat astroglial cell line (C6). The C6 cell death induced by Aβ was decreased by OBHS (1 μM) treatment for 45 min...
April 4, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28368610/bax-activation-blocks-self-renewal-and-induces-apoptosis-of-human-glioblastoma-stem-cells
#18
Simona Daniele, Deborah Pietrobono, Barbara Costa, Mariateresa Giustiniano, Valeria La Pietra, Chiara Giacomelli, Giuseppe La Regina, Romano Silvestri, Sabrina Taliani, Maria Letizia Trincavelli, Federico Da Settimo, Ettore Novellino, Claudia Martini, Luciana Marinelli
Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inhibition of pro-apoptotic ones, which help to escape apoptosis. Among pro-apoptotic inducers, the Bcl-2 family protein Bax has recently emerged as a promising new target in cancer therapy along with first BAX activators (BAM7, Compound 106, and SMBA1)...
April 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28367271/nicotinamide-adenine-dinucleotide-protects-against-spinal-cord-ischemia-reperfusion-injury-induced-apoptosis-by-blocking-autophagy
#19
Lei Xie, Sifei Yu, Zhenfei Wang, Kai Yang, Zhuochao Liu, Changwei Li, Yu Liang
The role of autophagy, neuroprotective mechanisms of nicotinamide adenine dinucleotide (NAD(+)), and their relationship in spinal cord ischemic reperfusion injury (SCIR) was assessed. Forty-eight Sprague-Dawley rats were divided into four groups: sham, ischemia reperfusion (I/R), 10 mg/kg NAD(+), and 75 mg/kg NAD(+). Western blotting, immunofluorescence, and immunohistochemistry were used to assess autophagy and apoptosis. Basso, Beattie, and Bresnahan (BBB) scores were used to assess neurological function...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28365156/mild-hypothermia-protects-against-oxygen-glucose-deprivation-reoxygenation-induced-apoptosis-via-the-wnt-%C3%AE-catenin-signaling-pathway-in-hippocampal-neurons
#20
Zhou Tianen, Yanran Liang, Longyuan Jiang, Tao Yu, Chaotao Zeng, Tao Enxiang
Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway...
March 29, 2017: Biochemical and Biophysical Research Communications
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