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https://www.readbyqxmd.com/read/28822990/%C3%AE-%C3%AE-mangostins-induces-autophagy-and-shows-synergistic-effectwith-gemcitabine-in-pancreatic-cancer-cell-lines
#1
Myoungjae Kim, Young-Won Chin, Eun Joo Lee
Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of α-mangostin (αM) and γ-mangostin (γM) extracted from the pericarp of Garcinia mangostana L.. Both αM and γM reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28821270/calmodulin-like-protein-3-is-an-estrogen-receptor-alpha-coregulator-for-gene-expression-and-drug-response-in-a-snp-estrogen-and-serm-dependent-fashion
#2
Sisi Qin, James N Ingle, Mohan Liu, Jia Yu, D Lawrence Wickerham, Michiaki Kubo, Richard M Weinshilboum, Liewei Wang
BACKGROUND: We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1...
August 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28817179/autophagy-induction-plays-a-protective-role-against-hypoxic-stress-in-human-dental-pulp-cells
#3
Sam-Young Park, Eun-Gene Sun, Yeonju Lee, Min-Seok Kim, Jae Hyung Kim, Won-Jae Kim, Ji-Yeon Jung
Human dental pulp exposed to hypoxic conditions induces cell death accompanied by autophagy. However, the role of hypoxia-induced autophagy in human dental pulp cells (HDPCs) is unclear. The present study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of HDPCs. Cobalt chloride (CoCl2 ) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis-related signal molecules, cleaved caspase-3 and PARP levels, were enhanced in CoCl2 -treated HDPCs. HDPCs exposed to CoCl2 also promoted autophagy, showing upregulated p62 and microtubule-associated protein 1 light chain 3 (LC3)-II levels, typical autophagic markers, and increased acidic autophagolysosomal vacuoles...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815640/in-vitro-genotoxicity-of-airborne-ni-np-in-air-liquid-interface
#4
Siiri Latvala, Daniel Vare, Hanna L Karlsson, Karine Elihn
Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni-NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni-NPs using a recently developed air-liquid interface exposure system. The wild-type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively...
August 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#5
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28810554/beneficial-effects-of-dried-pomegranate-juice-concentrated-powder-on-ultraviolet-b-induced-skin-photoaging-in-hairless-mice
#6
Su-Jin Kang, Beom-Rak Choi, Seung-Hee Kim, Hae-Yeon Yi, Hye-Rim Park, Chang-Hyun Song, Sae-Kwang Ku, Young-Joon Lee
The present study investigated the anti-aging effects of pomegranate juice concentrated powder (PCP) in hairless mice following 15 weeks of UVB irradiation (three times a week; 0.18 J/cm(2)). Skin moisturizing effects were evaluated through skin water, collagen type I and hyaluronan contents, as well as collagen type I and hyaluronan synthesis-related transcript levels. Wrinkle formation and edema scores (skin weights) were also assessed, along with skin matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13 transcript levels...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808311/antitumor-properties-of-coenzyme-q0-against-human-ovarian-carcinoma-cells-via-induction-of-ros-mediated-apoptosis-and-cytoprotective-autophagy
#7
You-Cheng Hseu, Tai-Jung Tsai, Mallikarjuna Korivi, Jer-Yuh Liu, Hui-Jye Chen, Chung-Ming Lin, Yi-Chun Shen, Hsin-Ling Yang
Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807902/h2av-facilitates-h3s10-phosphorylation-but-is-not-required-for-heat-shock-induced-chromatin-decondensation-or-transcriptional-elongation
#8
Yeran Li, Chao Wang, Weili Cai, Saheli Sengupta, Michael Zavortink, Huai Deng, Jack Girton, Jørgen Johansen, Kristen M Johansen
A model has been proposed where JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation to occur. However, here we show that while H3S10 phosphorylation is indeed compromised in the H2Av null mutant we find that chromatin decondensation at heat shock loci is unaffected both in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of Pol II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Av and JIL-1 null mutants...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28806997/stathmin-is-overexpressed-and-regulated-by-mutant-p53-in-oral-squamous-cell-carcinoma
#9
Hai-Long Ma, Shu-Fang Jin, Wu-Tong Ju, Yong Fu, Yao-Yao Tu, Li-Zhen Wang, Jiang-Li, Zhi-Yuan Zhang, Lai-Ping Zhong
BACKGROUND: The aim of this study was to investigate the oncogenic function and regulatory mechanism of stathmin in oral squamous cell carcinoma (OSCC). METHODS: Two-dimensional electrophoresis and liquid chromatography-tandem mass chromatography were applied to screen differentiated proteins during carcinogenesis in OSCC. Cell Counting Kit-8 (CCK-8) assays, colony formation, migration, flow cytometry, immunofluorescence and a xenograft model were used to detect the function of stathmin...
August 14, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28804761/unfolding-of-core-nucleosomes-by-parp-1-revealed-by-spfret-microscopy
#10
Daniel C Sultanov, Nadezhda S Gerasimova, Kseniya S Kudryashova, Natalya V Maluchenko, Elena Y Kotova, Marie-France Langelier, John M Pascal, Mikhail P Kirpichnikov, Alexey V Feofanov, Vasily M Studitsky
DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose)polymerase 1) increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer) microscopy...
2017: AIMS Genetics
https://www.readbyqxmd.com/read/28804538/exendin-4-assisted-adipose-derived-mesenchymal-stem-cell-therapy-protects-renal-function-against-co-existing-acute-kidney-ischemia-reperfusion-injury-and-severe-sepsis-syndrome-in-rat
#11
Pei-Hsun Sung, Hsin-Ju Chiang, Christopher Glenn Wallace, Chih-Chao Yang, Yen-Ta Chen, Kuan-Hung Chen, Chih-Hung Chen, Pei-Lin Shao, Yung-Lung Chen, Sarah Chua, Han-Tan Chai, Yi-Ling Chen, Tien-Hung Huang, Hon-Kan Yip, Mel S Lee
This study tested the hypothesis that combined therapy with exendin-4 (Ex4) and autologous adipose-derived mesenchymal stem cells (ADMSCs) was superior to either alone for protecting renal function against acute kidney ischemia-reperfusion (IR; 40-min ischemia/27-h reperfusion) injury when complicated by sepsis syndrome (SS; by cecal-ligation-puncture). Adult-male Sprague-Dawley rats (n=40) were equally divided into group 1 (sham-control), group 2 (IR-SS), group 3 (IR-SS + Ex4, 10 μg/kg subcutaneously 30 min after reperfusion and daily for 3 days), group 4 [IR-SS + ADMSC (1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28802212/pharmacophore-based-design-of-some-multi-targeted-compounds-targeted-against-pathways-of-diabetic-complications
#12
Navriti Chadha, Om Silakari
Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc...
July 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28801290/-quinalizarin-induces-apoptosis-in-gastric-cancer-ags-cells-via-mapk-and-akt-signaling-pathway
#13
Chang Liu, Ying-Hua Luo, Xian-Ji Piao, Yue Wang, Ling-Qi Meng, Hao Wang, Jia-Ru Wang, Yi Zhang, Jin-Qian Li, Cheng-Hao Jin
OBJECTIVE: To investigate quinalizarin-induced apoptosis in gastric cancer cells in vitro and explore the molecular mechanisms. METHODS: MTT assay was used to determine the cytotoxic effects of quinalizarin on human gastric cancer AGS, MKN-28 and MKN-45 cells. Annexin V-FITC/PI staining and flow cytometry were used to assess quinalizarin-induced apoptosis in AGS cells and its effect on intracellular ROS levels; the expression levels of apoptotic proteins in the cells were determined with Western blotting...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28800882/salvianolic-acid-b-inhibits-intermittent-high-glucose-induced-ins-1-cell-apoptosis-through-regulation-of-bcl-2-proteins-and-mitochondrial-membrane-potential
#14
Shanjun Tao, Younan Ren, Haowen Zheng, Mengqiu Zhao, Xu Zhang, Yuanmei Zhu, Jieren Yang, Shuguo Zheng
Blood glucose fluctuations, also referred to as intermittent high glucose, have been validated to be more harmful than sustained high glucose in exacerbating pancreatic dysfunction by inducing β cell apoptosis. Salvianolic acid B (Sal B), an aqueous component of Salvia miltiorrhiza, has been proved beneficial to pancreatic islet function in diabetes, but the underlying mechanisms remain to be elucidated. The present study investigated the protective effect of Sal B on INS-1 cells exposed to intermittent high glucose and the possible mechanisms implicated...
August 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28797568/the-combination-of-a-966492-and-topotecan-for-effective-radiosensitization-on-glioblastoma-spheroids
#15
Fereshteh Koosha, Ali Neshasteh-Riz, Abbas Takavar, Nazila Eyvazzadeh, Zohreh Mazaheri, Samira Eynali, Mehdi Mousavi
Radiotherapy is one of the modalities in the treatment of glioblastoma patients, but glioma tumors are resistant to radiation and also chemotherapy drugs. Thus, researchers are investigating drugs which have radiosensitization capabilities in order to improve radiotherapy. PARP enzymes and topoisomerase I enzymes have a critical role in repairing DNA damage in tumor cells. Thus, inhibiting activity of these enzymes helps stop DNA damage repair and increase DSB lethal damages. In the current study, we investigated the combination of TPT as a topoisomerase I inhibitor, and A-966492 as a novel PARP inhibitor for further radiosensitization...
August 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28797284/gambogic-acid-sensitizes-gemcitabine-efficacy-in-pancreatic-cancer-by-reducing-the-expression-of-ribonucleotide-reductase-subunit-m2-rrm2
#16
Guanggai Xia, Hongcheng Wang, Ziliang Song, Qingcai Meng, Xiuyan Huang, Xinyu Huang
BACKGROUND: Pancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer...
August 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#17
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791810/cytotoxicity-of-anticancer-drugs-and-pj-34-poly-adp-ribose-polymerase-1-parp-1-inhibitor-on-hl-60-and-jurkat-cells
#18
Maciej Stępnik, Sylwia Spryszyńska, Anna Gorzkiewicz, Magdalena Ferlińska
BACKGROUND: The majority of the clinical trials with poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors were conducted or are ongoing in patients with solid tumors, while trials with leukemia patients are less frequent. Surprisingly scarce data is available on the combinatory effects of PARP inhibitors with DNA damaging antitumor drugs in leukemic cells (primary cells or established lines). OBJECTIVES: The aim of the present study was to assess the effect of PJ-34 (PARP-1 inhibitor) on the cytotoxicity of different antileukemic drugs with different DNA damaging mechanisms and potency (doxorubicin, etoposide, cytarabine and chlorambucil) in human leukemic Jurkat and HL-60 cells...
May 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28790837/rucaparib-the-past-present-and-future-of-a-newly-approved-parp-inhibitor-for-ovarian-cancer
#19
REVIEW
L E Dockery, C C Gunderson, K N Moore
Rucaparib camsylate (CO-338, AG-014699, PF-01367338) is a potent PARP-1, PARP-2, and PARP-3 inhibitor. Phase I and II studies demonstrated clinical efficacy in both BRCA-mutated (inclusive of germline and somatic) ovarian tumors and ovarian tumors with homologous recombination deficiency (HRD) loss of heterozygosity (LOH). Rucaparib has received the US Food and Drug Administration (FDA) approval for patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790402/h-ferritin-nanocaged-olaparib-a-promising-choice-for-both-brca-mutated-and-sporadic-triple-negative-breast-cancer
#20
S Mazzucchelli, M Truffi, F Baccarini, M Beretta, L Sorrentino, M Bellini, M A Rizzuto, R Ottria, A Ravelli, P Ciuffreda, D Prosperi, F Corsi
Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells...
August 8, 2017: Scientific Reports
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