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https://www.readbyqxmd.com/read/27906173/sensitivity-of-gbm-cells-to-camp-agonist-mediated-apoptosis-correlates-with-cd44-expression-and-agonist-resistance-with-mapk-signaling
#1
Paul M Daniel, Gulay Filiz, Theo Mantamadiotis
In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27897092/an-investigation-on-intermolecular-interaction-between-bis-indolyl-methane-and-hsa-and-bsa-using-multi-technique-methods
#2
Hamid Dezhampanah, Roghaye Firouzi
Bis(indolyl)methane (BIM) as one of the main active components of anticancer and antibacterial drugs is applied in medicinal and extensive area of chemistry. In this research interaction of human and bovine serum albumins, as drug carriers with BIM was investigated using spectroscopy methods and molecular modeling study. The fluorescence quenching measurements at the rage of 293 to 310 K revealed that the quenching mechanisms for human and bovine serum albumins are static and dynamic processes, respectively...
November 29, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#3
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27892697/allium-roseum-l-extract-exerts-potent-suppressive-activities-on-chronic-myeloid-leukemia-k562-cell-viability-through-the-inhibition-of-bcr-abl-pi3k-akt-and-erk1-2-pathways-and-the-abrogation-of-vegf-secretion
#4
Soumaya Souid, Hanen Najjaa, Ichrak Riahi-Chebbi, Meriam Haoues, Mohamed Neffati, Ingrid Arnault, Jacques Auger, Habib Karoui, Makram Essafi, Khadija Essafi-Benkhadir
Use of plant extracts, alone or combined to the current chemotherapy as chemosensitizers, has emerged as a promising strategy to overcome tumor drug resistance. Here, we investigated the anticancer activity of Allium roseum L. extracts, a wild edible species in North Africa, on human Chronic Myeloid Leukemia (CML) K562 cells. The dehydrated aqueous extract (DAE) disturbed the cell cycle progression and induced the apoptosis of K562 cells. Chemical analysis of DAE showed a diversity of organosulfur compounds S-alk(en)yl-cysteine sulfoxides (RCSO) and high amount of allicin, suggesting that such molecule may be behind its antitumor effect...
November 28, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90-rasgrp1-and-hsp90-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#5
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here we show that trichostatin A, romidepsin, and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine, and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888798/mir-103-inhibits-proliferation-and-sensitizes-hemopoietic-tumor-cells-for-glucocorticoid-induced-apoptosis
#6
Shlomit Kfir-Erenfeld, Noa Haggiag, Moshe Biton, Polina Stepensky, Nathalie Assayag-Asherie, Eitan Yefenof
Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888447/the-regulation-of-the-mitochondrial-apoptotic-pathway-by-glucocorticoid-receptor-in-collaboration-with-bcl-2-family-proteins-in-developing-t-cells
#7
Lilla Prenek, Ferenc Boldizsár, Réka Kugyelka, Emese Ugor, Gergely Berta, Péter Németh, Timea Berki
Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity...
November 26, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27888102/the-phosphatidyl-inositol-3-kinase-pathway-does-not-suppress-activation-of-the-arf-and-bim-genes-by-deregulated-e2f1-activity
#8
Kenta Kurayoshi, Junko Okuno, Eiko Ozono, Ritsuko Iwanaga, Andrew P Bradford, Kazuyuki Kugawa, Keigo Araki, Kiyoshi Ohtani
The transcription factor E2F plays crucial roles in tumor suppression by activating pro-apoptotic genes such as the tumor suppressor ARF. The regulation of the ARF gene is distinct from that of growth-related E2F targets, in that it is specifically activated by deregulated E2F activity, induced by over-expression of E2F or forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. The phosphatidyl inositol 3 kinase (PI3K) pathway was reported to suppress expression of some atypical pro-apoptotic genes by over-expressed E2F1...
November 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27887917/microrna-136-inhibits-cancer-stem-cell-activity-and-enhances-the-anti-tumor-effect-of-paclitaxel-against-chemoresistant-ovarian-cancer-cells-by-targeting-notch3
#9
Ju-Yeon Jeong, Hae-Youn Kang, Tae-Heon Kim, Gwang-Il Kim, Jin-Hyung Huh, Ah-Young Kwon, Se-Wha Kim, Sang-Geun Jung, Hee-Jung An
To identify microRNAs (miRNAs) regulating Notch3 expression in association with paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was significantly downregulated in OSC tissues relative to normal control tissues, and low expression of miR-136 correlated with poor overall in ovarian cancer patients. Artificial miR-136 overexpression significantly reduced cell viability, proliferation, CSC spheroid formation, and angiogenesis, and increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects of paclitaxel alone...
November 22, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27882343/proapoptotic-protein-bim-attenuates-estrogen-enhanced-survival-in-lymphangioleiomyomatosis
#10
Chenggang Li, Na Li, Xiaolei Liu, Erik Y Zhang, Yang Sun, Kouhei Masuda, Jing Li, Julia Sun, Tasha Morrison, Xiangke Li, Yuanguang Chen, Jiang Wang, Nagla A Karim, Yi Zhang, John Blenis, Mauricio J Reginato, Elizabeth P Henske, Jane J Yu
Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient-derived cells' resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27881235/elucidating-the-role-of-the-foxo3a-transcription-factor-in-the-igf-1-induced-migration-and-invasion-of-uveal-melanoma-cancer-cells
#11
Fengxia Yan, Rifang Liao, Mohd Farhan, Tinghuai Wang, Jiashu Chen, Zhong Wang, Peter J Little, Wenhua Zheng
Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis...
November 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27873035/dmfc-3-5-dimethyl-7-h-furo-3-2-g-chromen-7-one-regulates-bim-to-trigger-bax-and-bak-activation-to-suppress-drug-resistant-human-hepatoma
#12
Jun Xiang, Zhe Wang, Qianqian Liu, Xia Li, Jianguo Sun, Kwok-Pui Fung, Feiyan Liu
3,5-Dimethyl-(7)H-furo[3,2-g]chromen-7-one (DMFC) is a coumarin derivative with anti-cancer activity against human hepatoma cells, but the mechanisms underlying DMFC function in cancer suppression is unknown. In this study, we aimed at elucidating the molecular mechanisms underlying DMFC anti-cancer activity and determining whether DMFC is effective in suppression of drug-resistant human hepatocellular carcinoma. We show here that DMFC effectively suppresses both the parent and the multidrug-resistant hepatoma cell growth in vitro and DMFC suppresses hepatoma cell growth at least in part through inducing tumor cell apoptosis...
November 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27866524/-effect-and-significance-of-bim-on-non-small-cell-lung-cancer
#13
Jingfang Wang, Tao Xin
B-cell lymphoma 2 interacting mediator of cell death (BIM) plays an important role in the progress of cell apoptosis. The lowering expression level or functional defect of which may have an negative effect on the efficacy of anticancer drugs and the prognosis of postoperative patients with non-small cell lung cancer (NSCLC). This review aims to summarize the structure and function of BIM, as well as the relationship between BIM and the therapeutic efficacy of NSCLC.
November 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#14
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27856324/mll-af4-binds-directly-to-a-bcl-2-specific-enhancer-and-modulates-h3k27-acetylation
#15
Laura Godfrey, Jon Kerry, Ross Thorne, Emmanouela Repapi, James O J Davies, Marta Tapia, Erica Ballabio, Jim R Hughes, Huimin Geng, Marina Konopleva, Thomas A Milne
Survival rates for children and adults carrying mutations in the Mixed Lineage Leukemia (MLL) gene continue to have a very poor prognosis. The most common MLL mutation in ALL is the t(4;11)(q21;q23) chromosome translocation that fuses MLL in frame with the AF4 gene producing MLL-AF4 and AF4-MLL fusion proteins. Previously, we demonstrated that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. Here, we perform a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
November 14, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27852740/temporal-expression-of-bim-limits-the-development-of-agonist-selected-thymocytes-and-skews-their-tcr%C3%AE-repertoire
#16
Kun-Po Li, Anke Fähnrich, Eron Roy, Carla M Cuda, H Leighton Grimes, Harris R Perlman, Kathrin Kalies, David A Hildeman
CD8αα TCRαβ(+) intestinal intraepithelial lymphocytes play a critical role in promoting intestinal homeostasis, although mechanisms controlling their development and peripheral homeostasis remain unclear. In this study, we examined the spatiotemporal role of Bim in the thymic selection of CD8αα precursors and the fate of these cells in the periphery. We found that T cell-specific expression of Bim during early/cortical, but not late/medullary, thymic development controls the agonist selection of CD8αα precursors and limits their private TCRβ repertoire...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27843613/mechanisms-of-resistance-to-egfr-targeted-drugs-lung-cancer
#17
REVIEW
Floriana Morgillo, Carminia Maria Della Corte, Morena Fasano, Fortunato Ciardiello
Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC...
2016: ESMO Open
https://www.readbyqxmd.com/read/27843137/pi3k%C3%AE-inhibition-elicits-anti-leukemic-effects-through-bim-dependent-apoptosis
#18
M J Carter, K L Cox, S J Blakemore, A H Turaj, R J Oldham, L N Dahal, S Tannheimer, F Forconi, G Packham, M S Cragg
PI3Kδ plays pivotal roles in the maintenance, proliferation, and survival of malignant B-lymphocytes. Although not curative, PI3Kδ inhibitors (PI3Kδi) demonstrate impressive clinical efficacy and, alongside other signaling inhibitors, are revolutionizing the treatment of hematological malignancies. However, only limited in vivo data are available regarding their mechanism of action. With the rising number of novel treatments, the challenge is to identify combinations that deliver curative regimes. A deeper understanding of the molecular mechanism is required to guide these selections...
November 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27836739/docosahexaenoic-acid-signaling-attenuates-the-proliferation-and-differentiation-of-bone-marrow-derived-osteoclast-precursors-and-promotes-apoptosis-in-mature-osteoclasts
#19
Hyun-Ju Kim, Boram Ohk, Hye Jin Yoon, Woo Youl Kang, Sook Jin Seong, Shin-Yoon Kim, Young-Ran Yoon
Docosahexaenoic acid (DHA), a component of omega-3 fatty acids, has been reported to protect against inflammatory bone diseases such as osteoporosis and rheumatoid arthritis. However, its exact mechanism in bone resorbing cells has not been elucidated. In this study, we investigated the effects and the molecular mechanism of DHA on the proliferation, differentiation, and survival of osteoclast lineage cells using mouse bone marrow-derived macrophages (BMMs). DHA suppressed the macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursors, BMMs, in a dose-dependent manner...
November 9, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27827850/interferon-%C3%AE-induces-the-apoptosis-of-cervical-cancer-hela-cells-by-activating-both-the-intrinsic-mitochondrial-pathway-and-endoplasmic-reticulum-stress-induced-pathway
#20
Wei-Ye Shi, Cheng Cao, Li Liu
The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types. However, the effect of IFN-α on cervical cancer remains unknown. In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells...
November 2, 2016: International Journal of Molecular Sciences
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