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https://www.readbyqxmd.com/read/28526868/chitosan-dextran-sulfate-coated-doxorubicin-loaded-plga-pva-nanoparticles-caused-apoptosis-in-doxorubicin-resistance-breast-cancer-cells-through-induction-of-dna-damage
#1
Sumit Siddharth, Anmada Nayak, Deepika Nayak, Birendra Kumar Bindhani, Chanakya Nath Kundu
To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522946/parthenolide-promotes-apoptotic-cell-death-and-inhibits-the-migration-and-invasion-of-sw620-cells
#2
Yu Chuan Liu, Se Lim Kim, Young Ran Park, Soo-Teik Lee, Sang Wook Kim
BACKGROUND/AIMS: Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells. METHODS: SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death...
April 2017: Intestinal Research
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#3
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522584/cooperative-targets-of-combined-mtor-hdac-inhibition-promote-myc-degradation
#4
John K Simmons, Aleksandra M Michalowski, Benjamin J Gamache, Wendy DuBois, Jyoti Patel, Ke Zhang, Joy Gary, Shuling Zhang, Snehal Gaikwad, Daniel Connors, Nicholas Watson, Elena Leon, Jin-Qiu Chen, W Michael Kuehl, Maxwell P Lee, Adriana Zingone, Ola Landgren, Peter Ordentlich, Jing Huang, Beverly A Mock
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents.  In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521246/synthesis-of-novel-dibenzoxanthene-derivatives-and-observation-of-apoptosis-in-human-hepatocellular-cancer-cells
#5
Hui-Hui Yang, Yun-Jun Liu, Xiu-Zhen Wang
We have synthesized dibenzoxanthene derivatives 2a-2i via nucleophilic substitution of methoxyl group and evaluated underlying antitumor molecular mechanism of target compounds. Compounds showed high cytotoxic activities against BEL-7402, A549, HeLa and MG-63 cancer cells in the µM range. These compounds inhibited the cell growth of BEL-7402 cells at S or G2/M phase. The compounds 2a-2i also induced the apoptosis of BEL-7402 cells. In addition, compounds enhanced the level of intramolecular ROS and decreased the mitochondrial membrane potential...
May 4, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28518135/rack1-depletion-in-the-ribosome-induces-selective-translation-for-non-canonical-autophagy
#6
Hag Dong Kim, EunBin Kong, YongJoong Kim, Jin-Soo Chang, Joon Kim
RACK1, which was first demonstrated as a substrate of PKCβ II, functions as a scaffold protein and associates with the 40S small ribosomal subunit. According to previous reports, ribosomal RACK1 was also suggested to control translation depending on the status in translating ribosome. We here show that RACK1 knockdown induces autophagy independent of upstream canonical factors such as Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating increased translation of these proteins...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28511583/deciphering-the-crucial-residues-involved-in-heterodimerization-of-bak-peptide-and-anti-apoptotic-proteins-for-apoptosis
#7
Parthiban Marimuthu, Kalaimathy Singaravelu
B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of apoptosis, function via mitochondrial outer membrane permeabilization. The family members are involved in several stages of apoptosis regulation. The overexpression of the anti-apoptotic proteins leads to several cancer pathological conditions. This overexpression is modulated or inhibited by heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the hydrophobic groove present at the surface of anti-apoptotic proteins. Additionally, the heterodimerization displayed differences in binding affinity profile among the pro-apoptotic peptides binding to anti-apoptotic proteins...
May 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28510655/mir-145-promoted-anoikis-resistance-in-tumor-endothelial-cells
#8
Kyoko Hida, Taisuke Kawamoto, Nako Maishi, Masahiro Morimoto, Kosuke Akiyama, Noritaka Ohga, Masanobu Shindoh, Nobuo Shinohara, Yasuhiro Hida
Tumor progression is dependent on tumor angiogenesis. We previously reported that the phenotype of tumor endothelial cells (TECs) is distinct from normal endothelial cells (NECs). Herein, we conducted a pathway analysis using a public TEC microarray database and identified several putative TEC-specific miRNAs. We found that miR-145 expression was upregulated in TECs and that miR-145 enhanced cell adhesion and anoikis resistance and upregulated Bcl-2 and Bcl-xl via ERK1/2in human microvascular endothelial cells...
May 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28507307/a-novel-indication-for-panobinostat-as-a-senolytic-drug-in-nsclc-and-hnscc
#9
Leleesha Samaraweera, Alfred Adomako, Alicia Rodriguez-Gabin, Hayley M McDaid
Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is interest in evaluating alternate dosing schedules and novel combinations of pano for the treatment of upper aerodigestive and lung malignancies; thus we evaluated it in combination with Taxol, a chemotherapeutic with activity in both diseases. Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to senescence rather than potentiation of cell death...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28504908/mammea-longifolia-planch-and-triana-fruit-extract-induces-cell-death-in-the-human-colon-cancer-cell-line-sw480-via-mitochondria-related-apoptosis-and-activation-of-p53
#10
Chunmei Li, Yoonhwa Jeong, Misook Kim
The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia) fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate dehydrogenase assays, respectively. One hundred μg/mL of the extract killed ∼82.4% of the cells; however, 2% of the death was related to necrosis. The morphological changes in M. longifolia-stimulated SW480 cells were observed directly by light microscopy...
May 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28503147/an-ethanolic-extract-of-ampelopsis-radix-exerts-anti-colorectal-cancer-effects-and-potently-inhibits-stat3-signaling-in-vitro
#11
Tao Su, Jing-Xuan Bai, Ying-Jie Chen, Xin-Ning Wang, Xiu-Qiong Fu, Ting Li, Hui Guo, Pei-Li Zhu, Yue Wang, Zhi-Ling Yu
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28501723/tangeretin-alters-neuronal-apoptosis-and-ameliorates-the-severity-of-seizures-in-experimental-epilepsy-induced-rats-by-modulating-apoptotic-protein-expressions-regulating-matrix-metalloproteinases-and-activating-the-pi3k-akt-cell-survival-pathway
#12
Xiao-Qian Guo, Yu-Ling Cao, Fang Hao, Zhong-Rui Yan, Mei-Ling Wang, Xue-Wu Liu
PURPOSE: Epilepsy is complex neural disarray categorized by recurring seizures. Despite recent advances in pharmacotherapies for epilepsy, its treatment remains a challenge due to the contrary effects of the drugs. As a result, the identification of novel anti-epileptic drugs (AEDs) with neuroprotective properties and few side effects is of great value. Thus, the present study assessed the treatment effects of tangeretin using a rat model of pilocarpine-induced epilepsy. MATERIALS AND METHODS: Separate groups of male Wistar rats received oral administrations of tangeretin at 50, 100, or 200mg/kg for 10 days and then, on the 10th day, they received an intraperitoneal injection of pilocarpine (30mg/kg)...
May 11, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28498799/dietary-luteolin-attenuates-chronic-liver-injury-induced-by-mercuric-chloride-via-the-nrf2-nf-%C3%AE%C2%BAb-p53-signaling-pathway-in-rats
#13
Haili Zhang, Xiao Tan, Daqian Yang, Jingjing Lu, Biying Liu, Ruiqi Baiyun, Zhigang Zhang
Mercury exposure is a common cause of metal poisoning which is biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. Luteolin, a phenolic compound found in many natural products, has multiple biological functions. Our study was aimed to explore the biological effects of luteolin in a liver injury model induced in rats by mercuric chloride (HgCl2). Criteria for injury included liver enzyme, glutathione and malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and reactive oxygen species levels...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498447/dec2-expression-antagonizes-cisplatin%C3%A2-induced-apoptosis-in-human-esophageal-squamous-cell-carcinoma
#14
Hidenobu Sato, Yunyan Wu, Yukio Kato, Qiang Liu, Hideaki Hirai, Tadashi Yoshizawa, Satoko Morohashi, Jun Watanabe, Hiroshi Kijima
Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix‑loop‑helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis‑related markers in human esophageal squamous cell carcinoma TE‑11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively...
May 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28494251/nitric-oxide-releasing-derivatives-of-brefeldin-a-as-potent-and-highly-selective-anticancer-agents
#15
Kangtao Tian, Fanxing Xu, Xiang Gao, Tong Han, Jia Li, Huaqi Pan, Linghe Zang, Dahong Li, Zhanlin Li, Takahiro Uchita, Ming Gao, Huiming Hua
A series of NO-donating mono- or diester derivatives of brefeldin A were designed, synthesized and biologically evaluated. Some derivatives exhibited potent antiproliferative activity with low IC50 values. The most potent NO-donating hybrid 13b exhibited stronger cytotoxicity against human prostate cancer PC-3 cells, human colon carcinoma HT-29 cells and human liver cancer HepG-2 cells than BFA with IC50 values of 25 nM, 160 nM and 180 nM, respectively. More importantly, compound 13b showed good selectivity between human normal and tumor liver cells with selectivity index of 33...
May 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28486788/the-long-unstructured-region-of-bcl-xl-modulates-its-structural-dynamics
#16
Prerna Priya, Atanu Maity, Shubhra Ghosh Dastidar
Bcl-xl protein has a long unstructured loop attached to its structured region which joins two helices. The necessity to have this unstructured segment in Bcl-xl is not yet understood. To what extent the unstructured segment can influence the dynamics of the structured region of protein, with potential to influence the function, has been investigated in this work. Molecular dynamics simulation and principal component analysis show how the loop affects the internal motions of the protein, particularly its ligand binding pocket...
May 9, 2017: Proteins
https://www.readbyqxmd.com/read/28481930/expression-of-human-bcl-xl-ser49-and-ser62-mutants-in-caenorhabditis-elegans-causes-germline-defects-and-aneuploidy
#17
Prasamit Saurav Baruah, Myriam Beauchemin, J Alexander Parker, Richard Bertrand
An interesting feature of Bcl-xL protein is the presence of an unstructured loop domain between α1 and α2 helices, a domain not essential for its anti-apoptotic function and absent in CED-9 protein. Within this domain, Bcl-xL undergoes dynamic phosphorylation and dephosphorylation at Ser49 and Ser62 during G2 and mitosis in human cells. Studies have revealed that when these residues are mutated, cells harbour mitotic defects, including chromosome mis-attachment, lagging, bridging and mis-segregation with, ultimately, chromosome instability and aneuploidy...
2017: PloS One
https://www.readbyqxmd.com/read/28481901/%C3%AE-lapachone-suppresses-the-lung-metastasis-of-melanoma-via-the-mapk-signaling-pathway
#18
Ji-Ye Kee, Yo-Han Han, Dae-Seung Kim, Jeong-Geon Mun, Seong-Hwan Park, Hong-Seob So, Sung-Joo Park, Raekil Park, Jae-Young Um, Seung-Heon Hong
β-Lapachone is a natural quinone compound from Lapacho trees, which has various pharmacological effects such as anti-bacterial, anti-fungal, anti-viral, and anti-inflammatory activities. However, the effect of β-lapachone on metastasis of melanoma cells is unclear. In this study, β-lapachone reduced cell viability of metastatic melanoma cancer cell lines B16F10 and B16BL6 through induction of apoptosis via the mitogen-activated protein kinase (MAPK) pathway. Additionally, flow cytometry results showed that β-lapachone increased DNA content in the G0/G1 phase of the cell cycle...
2017: PloS One
https://www.readbyqxmd.com/read/28479926/oral-administration-of-tualang-and-manuka-honeys-modulates-breast-cancer-progression-in-sprague-dawley-rats-model
#19
Sarfraz Ahmed, Siti Amrah Sulaiman, Nor Hayati Othman
Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10-12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28479604/codelivery-of-dihydroartemisinin-and-doxorubicin-in-mannosylated-liposomes-for-drug-resistant-colon-cancer-therapy
#20
Xue-Jia Kang, Hui-Yuan Wang, Hui-Ge Peng, Bin-Fan Chen, Wen-Yuan Zhang, Ai-Hua Wu, Qin Xu, Yong-Zhuo Huang
Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes)...
May 8, 2017: Acta Pharmacologica Sinica
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