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https://www.readbyqxmd.com/read/29103194/astragalus-polysaccharides-increase-the-sensitivity-of-skov3-cells-to-cisplatin
#1
Caihong Li, Li Hong, Cheng Liu, Jie Min, Ming Hu, Wenjun Guo
BACKGROUND: Multidrug resistance in malignant tumours hinders the treatment of tumours. Studies showed that astragalus polysaccharides (APS), one major active ingredient of astragalus, enhanced the sensitivity of non-small cell lung cancer and liver cancer cells to chemotherapeutic drug. However, the effect of APS on ovarian cancer is still unclear. In this study, we will examine the sensitizing effect of APS on SKOV3 cells to cisplatin and explore the possible mechanism. METHODS: MTT assay was employed to examine the viability of SKOV3 after treatment with APS and cisplatin...
November 4, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29100331/targeting-signaling-and-apoptotic-pathways-involved-in-chemotherapeutic-drug-resistance-of-hematopoietic-cells
#2
Stephen L Abrams, Peter P Ruvolo, Vivian R Ruvolo, Giovanni Ligresti, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Agostino Tafuri, Linda S Steelman, Saverio Candido, Massimo Libra, James A McCubrey
A critical problem in leukemia as well as other cancer therapies is the development of chemotherapeutic drug-resistance. We have developed models of hematopoietic drug resistance that are based on expression of dominant-negative TP53 [TP53 (DN)] or constitutively-active MEK1 [MEK1(CA)] oncogenes in the presence of chemotherapeutic drugs. In human cancer, functional TP53 activity is often lost in human cancers. Also, activation of the Raf/MEK/ERK pathway frequently occurs due to mutations/amplification of upstream components of this and other interacting pathways...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093665/pi3k-and-inhibitor-of-apoptosis-proteins-modulate-gentamicin-induced-hair-cell-death-in-the-zebrafish-lateral-line
#3
Heather Wiedenhoft, Lauren Hayashi, Allison B Coffin
Inner ear hair cell death leads to sensorineural hearing loss and can be a direct consequence of aminoglycoside antibiotic treatment. Aminoglycosides such as gentamicin are effective therapy for serious Gram-negative bacterial infections such as some forms of meningitis, pneumonia, and sepsis. Aminoglycosides enter hair cells through mechanotransduction channels at the apical end of hair bundles and initiate intrinsic cell death cascades, but the precise cell signaling that leads to hair cell death is incompletely understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29091882/incretin-hormones-receptor-signaling-plays-the-key-role-in-antidiabetic-potential-of-pty-2-against-stz-induced-pancreatitis
#4
Shivani Srivastava, Priya Shree, Harsh Pandey, Yamini Bhusan Tripathi
AIMS: Incretin therapy is one of the most potential approaches in the treatment of diabetes. In contrast to markedly available drugs, the herbal incretin modulators have lesser side effects with low economic cost. The main aim of this work was to analyze the potential of previously reported DPPIV inhibitor, aqueous extract of Pueraria tuberosa tubers (PTY-2) as incretin hormones receptor agonist against streptozotocin (STZ)-induced diabetes. METHODS: Chronic diabetes was induced with STZ (65mg/kg bw) in rats for 60days and grouped into diabetic control and PTY-2...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29072699/cited2-affects-leukemic-cell-survival-by-interfering-with-p53-activation
#5
Katharina Mattes, Gerbrig Berger, Marjan Geugien, Edo Vellenga, Hein Schepers
CITED2 (CBP/p300-interacting-transactivator-with-an-ED-rich-tail 2) is a regulator of the acetyltransferase CBP/p300 and elevated CITED2 levels are shown in a number of acute myeloid leukemia (AML). To study the in vivo role of CITED2 in AML maintenance, AML cells were transduced with a lentiviral construct for RNAi-mediated knockdown of CITED2. Mice transplanted with CITED2-knockdown AML cells (n=4) had a significantly longer survival compared to mice transplanted with control AML cells (P<0.02). In vitro, the reduction of CITED2 resulted in increased p53-mediated apoptosis and CDKN1A expression, whereas BCL2 levels were reduced...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29072681/demethylzeylasteral-inhibits-cell-proliferation-and-induces-apoptosis-through-suppressing-mcl1-in-melanoma-cells
#6
Yuzu Zhao, Jiang He, Jun Li, Xingzhi Peng, Xianxing Wang, Zhen Dong, Erhu Zhao, Yaling Liu, Zonghui Wu, Hongjuan Cui
Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29065794/prolonged-exposure-of-resveratrol-induces-reactive-superoxide-species-independent-apoptosis-in-murine-prostate-cells
#7
Sanjay Kumar, James Stokes, Udai P Singh, Karyn Scissum-Gunn, Rajesh Singh, Upender Manne, Manoj K Mishra
Nitric oxide, a signaling molecule, inhibits mitochondrial respiration by binding with cytochrome c oxidase, resulting in elevated production of reactive superoxide species (reactive oxygen and nitrogen) in the mitochondria and increased susceptibility to cell death. Generation of mitochondrial superoxide species can be suppressed by natural compounds such as resveratrol, a dietary polyphenol found in the skin of red fruits. In various cancer cells, resveratrol shows anti-oxidant and cancer preventive properties...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29063678/molecular-profiling-and-combinatorial-activity-of-cct068127-a-potent-cdk2-and-cdk9-inhibitor
#8
Steven R Whittaker, Clare Barlow, Mathew P Martin, Caterina Mancusi, Steve Wagner, Annette Self, Elaine Barrie, Robert Te Poele, Swee Sharp, Nathan Brown, Stuart Wilson, Wayne Jackson, Peter M Fischer, Paul A Clarke, Michael I Walton, Edward McDonald, Julian Blagg, Martin Noble, Michelle D Garrett, Paul Workman
Deregulation of the cyclin-dependent kinases (CDKs) has been implicated in the pathogenesis of multiple cancer types. Consequently, CDKs have garnered intense interest as therapeutic targets for the treatment of cancer. We describe herein the molecular and cellular effects of CCT068127, a novel inhibitor of CDK2 and CDK9. Optimised from the purine template of seliciclib, CCT068127 exhibits greater potency and selectivity against purified CDK2 and CDK9 and superior antiproliferative activity against human colon cancer and melanoma cell lines...
October 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29062236/neat1-regulates-cell-proliferation-and-apoptosis-of-ovarian-cancer-by-mir-34a-5p-bcl2
#9
Nan Ding, Haiying Wu, Tao Tao, Erxuan Peng
BACKGROUND: Nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to act as a tumor inhibitor in many cancers. However, the role of NEAT1 in the development of ovarian cancer (OC) remains far from being elaborated. Hence, the aim of this study is to investigate the expression and function of NEAT1 in OC. MATERIALS AND METHODS: The expression level of NEAT1 was determined by quantitative real-time polymerase chain reaction in OC cell lines. MTT assay, caspase-3 activity assay, and flow cytometry analysis were conducted to investigate the effects of NEAT1, miR-34a-5p, or B-cell lymphoma-2 (BCL2) on OC cell proliferation and apoptosis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29048629/inhibition-of-neuroblastoma-proliferation-by-pf-3758309-a-small-molecule-inhibitor-that-targets-p21-activated-kinase-4
#10
Zhiheng Li, Xiaolu Li, Lixiao Xu, Yanfang Tao, Chun Yang, Xiaolan Chen, Fang Fang, Yi Wu, Xin Ding, He Zhao, Mei Li, Guanghui Qian, Yunyun Xu, Junli Ren, Weiwei Du, Jian Wang, Jun Lu, Shaoyan Hu, Jian Pan
Neuroblastoma is the most common extracranial solid childhood tumor. Despite the availability of advanced multimodal therapy, high-risk patients still have low survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and proliferation. However, the role of PAK4 in neuroblastoma remains unclear. In the present study, we demonstrated that PAK4 was overexpressed in neuroblastoma tissues and was correlated with tumor malignance and prognosis...
September 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29045843/high-throughput-functional-genetic-and-compound-screens-identify-targets-for-senescence-induction-in-cancer
#11
Liqin Wang, Rodrigo Leite de Oliveira, Cun Wang, João M Fernandes Neto, Sara Mainardi, Bastiaan Evers, Cor Lieftink, Ben Morris, Fleur Jochems, Lisa Willemsen, Roderick L Beijersbergen, René Bernards
Senescence is a proliferation arrest that can result from a variety of stresses. Cancer cells can also undergo senescence, but the stresses that provoke cancer cells to undergo senescence are unclear. Here, we use both functional genetic and compound screens in cancer cells harboring a reporter that is activated during senescence to find targets that induce senescence. We show that suppression of the SWI/SNF component SMARCB1 induces senescence in melanoma through strong activation of the MAP kinase pathway...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29040978/hydrogen-rich-saline-attenuates-brain-injury-induced-by-cardiopulmonary-bypass-and-inhibits-microvascular-endothelial-cell-apoptosis-via-the-pi3k-akt-gsk3%C3%AE-signaling-pathway-in-rats
#12
Keyan Chen, Nan Wang, Yugang Diao, Wanwei Dong, YingJie Sun, Lidan Liu, Xiuying Wu
BACKGROUND/AIMS: Cardiopulmonary bypass (CPB) is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. METHODS: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB) was used to assess permeability of the blood-brain barrier (BBB); HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT -PCR analyses of brain tissue and neurons...
October 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#13
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in MM cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase I study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28987383/hsp90-inhibitor-nvp-auy922-enhances-the-anti-cancer-effect-of-bcl-2-inhibitor-abt-737-in-small-cell-lung-cancer-expressing-bcl-2
#14
Hannah Yang, Mi-Hee Lee, Intae Park, Hanwool Jeon, Junyoung Choi, Seyoung Seo, Sang-We Kim, Gou Young Koh, Kang-Seo Park, Dae Ho Lee
Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC...
October 4, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28984869/bcl2-and-mir-15-16-from-gene-discovery-to-treatment
#15
REVIEW
Yuri Pekarsky, Veronica Balatti, Carlo M Croce
In 1984, we investigated the t(14;18) chromosomal translocations that frequently occur in patients with follicular lymphoma. We first identified a locus on chromosome 18 involved in these translocations with the chromosome 14 containing the immunoglobulin heavy chain locus. Within this region on chromosome 18, we then discovered a gene that we called BCL2, which was activated by the translocations. Since that time, many studies determined that BCL2 is one of the most important oncogenes involved in cancer by inhibiting apoptosis...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28982310/the-dipeptidyl-peptidase-iv-inhibitor-gemigliptin-alone-or-in-combination-with-nvp-auy922-has-a-cytotoxic-activity-in-thyroid-carcinoma-cells
#16
Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
The effect of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the heat shock protein 90 inhibitor NVP-AUY922 (AUY922) on survival of thyroid carcinoma cells was elucidated. The SW1736 and TPC-1 human thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, cytotoxic activity, the percentage of apoptotic cells, and mitochondrial membrane potential were measured. To evaluate the combined effect of gemigliptin with AUY922, the interactions were estimated by calculating combination index...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28981117/trehalose-ameliorates-oxidative-stress-mediated-mitochondrial-dysfunction-and-er-stress-via-selective-autophagy-stimulation-and-autophagic-flux-restoration-in-osteoarthritis-development
#17
Qian Tang, Gang Zheng, Zhenhua Feng, Yu Chen, Yiting Lou, Chenggui Wang, Xiaolei Zhang, Yu Zhang, Huazi Xu, Ping Shang, Haixiao Liu
Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28975995/mir-146a-inhibits-proliferation-and-induces-apoptosis-in-murine-osteoblastic-mc3t3-e1-by-regulating-bcl2
#18
B Zhang, J Yi, C-L Zhang, Q-H Zhang, J-F Xu, H-Q Shen, D-W Ge
OBJECTIVE: The dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of hormone-induced osteonecrosis of femoral head (ONFH). The research aimed to explore the regulatory role of miR-146a in dexamethasone (DEX)-induced proliferation and apoptosis change in MC3T3-E1 cells from murine osteoblastic. MATERIAL AND METHODS: In this study, MC3T3-E1 was co-cultured with 10-7 DEX for 6 h, then RT-PCR was employed to test the expression level of miR-146a and Bcl2...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28974930/induction-of-mkp-1-and-nuclear-translocation-of-nrf2-by-limonoids-from-khaya-grandifoliola-c-dc-protect-l-02-hepatocytes-against-acetaminophen-induced-hepatotoxicity
#19
Arnaud F Kouam, Fei Yuan, Frédéric N Njayou, Hongtao He, Roméo F Tsayem, Babayemi O Oladejo, Fuhang Song, Paul F Moundipa, George F Gao
Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports showing the hepatoprotective molecular mechanism of the plant are lacking. The aim of this study was therefore to identify compounds from the plant bearing hepatoprotective activity and the related molecular mechanism by assessing their effects against acetaminophen (APAP)-induced hepatotoxicity in normal human liver L-02 cells line...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28972015/synergy-of-bcl2-and-histone-deacetylase-inhibition-against-leukemic-cells-from-cutaneous-t-cell-lymphoma-patients
#20
Benoit M Cyrenne, Julia Lewis, Jason Weed, Kacie Carlson, Fatima N Mirza, Francine Foss, Michael Girardi
The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the anti-apoptotic mediator BCL2 as a potential therapeutic target...
October 2, 2017: Blood
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