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Withaferin A

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https://www.readbyqxmd.com/read/28782635/withaferin-a-induced-impaired-autophagy-and-unfolded-protein-response-in-human-breast-cancer-cell-lines-mcf-7-and-mda-mb-231
#1
Kamalini Ghosh, Soumasree De, Srimoyee Mukherjee, Sayantani Das, Amar Nath Ghosh, Sumita Bandyopadhyay Sengupta
The autophagy-lysosome pathway and the ubiquitin-proteasome systems are the two major routes for eukaryotic intracellular protein clearance. Cancerous cells often display elevated protein synthesis and byproduct disposal, thus, inhibition of the protein degradation pathways became an emerging approach for cancer therapy. The present study revealed that withaferin-A (WA), the biologically active withanolide derived from Withania somnifera, initially induced formation of autophagosomes in human breast cancer cell-lines, MCF-7 and MDA-MB-231...
August 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28694686/molecular-docking-qsar-and-admet-studies-of-withanolide-analogs-against-breast-cancer
#2
Dharmendra K Yadav, Surendra Kumar, Saloni, Harpreet Singh, Mi-Hyun Kim, Praveen Sharma, Sanjeev Misra, Feroz Khan
Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian traditional practice of medicine. Withanolides are steroidal lactones (highly oxygenated C-28 phytochemicals) and have been reported to exhibit immunomodulatory, anticancer and other activities. In the present study, a quantitative structure activity relationship (QSAR) model was developed by a forward stepwise multiple linear regression method to predict the activity of withanolide analogs against human breast cancer...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28693185/withaferin-a-inhibits-the-proliferation-of-gastric-cancer-cells-by-inducing-g2-m-cell-cycle-arrest-and-apoptosis
#3
Green Kim, Tae-Hyoun Kim, Eun-Ha Hwang, Kyu-Tae Chang, Jung Joo Hong, Jong-Hwan Park
Human gastric adenocarcinoma (AGS) is one of the most common types of malignant tumor and the third-leading cause of tumor-associated mortality worldwide. Withaferin A (WA), a steroidal lactone derived from Withania somnifera, exhibits antitumor activity in a variety of cancer models. However, to the best of our knowledge, the direct effect of WA on AGS cells has not previously been determined. The present study investigated the effects of WA on the proliferation and metastatic activity of AGS cells. WA exerted a dose-dependent cytotoxic effect on AGS cells...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28688542/evaluation-of-apoptotic-activity-of-withania-coagulans-methanolic-extract-against-human-breast-cancer-and-vero-cell-lines
#4
Rumana Ahmad, Afreen Fatima, A N Srivastava, Mohsin Ali Khan
BACKGROUND: The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal and Withania coagulans Dunal have been documented in folklore as panaceas for various ailments since time immemorial. W. coagulans (WC), commonly called as Indian cheese maker is used for fermenting milk for cheese production in various parts of India. OBJECTIVES: In the study, in vitro cytotoxicity of methanolic extract of dried fruits (berries) of WC was evaluated in a dose dependent manner using trypan blue dye exclusion method against human breast cancer cell line MDA-MB-231 and normal kidney epithelial cell line Vero in the range 20-200 μg/ml...
July 6, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/28686599/flux-balance-analysis-predicts-warburg-like-effects-of-mouse-hepatocyte-deficient-in-mir-122a
#5
Hua-Qing Wu, Mei-Ling Cheng, Jin-Mei Lai, Hsuan-Hui Wu, Meng-Chun Chen, Wen-Huan Liu, Wu-Hsiung Wu, Peter Mu-Hsin Chang, Chi-Ying F Huang, Ann-Ping Tsou, Ming-Shi Shiao, Feng-Sheng Wang
The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122) plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a-/-) to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a-/-mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28681243/synergistic-inhibition-of-glioma-cell-proliferation-by-withaferin-a-and-tumor-treating-fields
#6
Edwin Chang, Christoph Pohling, Nooshin Beygui, Chirag B Patel, Jarrett Rosenberg, Dong Ho Ha, Sanjiv S Gambhir
Glioblastoma (GBM) is the most aggressive and lethal form of brain cancer. Standard therapies are non-specific and often of limited effectiveness; thus, efforts are underway to uncover novel, unorthodox therapies against GBM. In previous studies, we investigated Withaferin A, a steroidal lactone from Ayurvedic medicine that inhibits proliferation in cancers including GBM. Another novel approach, tumor treating fields (TTFields), is thought to disrupt mitotic spindle formation and stymie proliferation of actively dividing cells...
July 5, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28676732/proinflammatory-cytokines-il-6-and-tnf-%C3%AE-increased-telomerase-activity-through-nf-%C3%AE%C2%BAb-stat1-stat3-activation-and-withaferin-a-inhibited-the-signaling-in-colorectal-cancer-cells
#7
Seyung S Chung, Yong Wu, Quincy Okobi, Debbie Adekoya, Mohammad Atefi, Orette Clarke, Pranabananda Dutta, Jaydutt V Vadgama
There are increasing evidences of proinflammatory cytokine involvement in cancer development. Here, we found that two cytokines, IL-6 and TNF-α, activated colorectal cancer cells to be more invasive and stem-like. Combined treatment of IL-6 and TNF-α phosphorylated transcription factors STAT3 in a synergistic manner. STAT3, STAT1, and NF-κB physically interacted upon the cytokine stimulation. STAT3 was bound to the promoter region of human telomerase reverse transcriptase (hTERT). IL-6 and TNF-α stimulation further enhanced STAT3 binding affinity...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28649699/a-wrky-transcription-factor-from-withania-somnifera-regulates-triterpenoid-withanolide-accumulation-and-biotic-stress-tolerance-through-modulation-of-phytosterol-and-defense-pathways
#8
Anup Kumar Singh, Sarma Rajeev Kumar, Varun Dwivedi, Avanish Rai, Shaifali Pal, Ajit K Shasany, Dinesh A Nagegowda
Withania somnifera produces pharmacologically important triterpenoid withanolides that are derived via phytosterol pathway; however, their biosynthesis and regulation remain to be elucidated. A jasmonate- and salicin-inducible WRKY transcription factor from W. somnifera (WsWRKY1) exhibiting correlation with withaferin A accumulation was functionally characterized employing virus-induced gene silencing and overexpression studies combined with transcript and metabolite analyses, and chromatin immunoprecipitation assay...
June 26, 2017: New Phytologist
https://www.readbyqxmd.com/read/28573248/withaferin-a-induces-apoptosis-in-rat-c6-glioma-cells-through-regulating-nf-kb-nuclear-translocation-and-activation-of-caspase-cascade
#9
Wei-Chen Hou, Xiao-Hui Miao, Lian-Jun Ma, Xiao-Xue Bai, Qun Liu, Lei Song
BACKGROUND: The demand for the chemopreventive drug from the plant source is increasing in recent times, owing to its various biological activities without any adverse effect. The intention of this current study was to examine the anti-glioma effect of Withaferin A (WFA) on C6 glioma cell line model. MATERIALS AND METHODS: C6 glioma cells were administrated with different concentration of WFA (50, 100, 200 and 500 μg/mL) and DMSO (control) group to examine its anti-proliferative, anti-inflammatory and pro-apoptotic activities...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28553635/alcoholic-fractions-f5-and-f6-from-withania-somnifera-leaves-show-a-potent-antileishmanial-and-immunomodulatory-activities-to-control-experimental-visceral-leishmaniasis
#10
Sambamurthy Chandrasekaran, Jalaja Veronica, Shyam Sundar, Radheshyam Maurya
Visceral leishmaniasis (VL) causes fatal life-threatening disease, if left untreated. The current drugs have various limitations; hence, natural products from medicinal plants are being focused in search of new drugs to treat leishmaniasis. The aim of the present study was to evaluate the antileishmanial and immunomodulatory activities of F5 and F6 alcoholic fractions from Withania somnifera leaves and purified withaferin-A in Leishmania donovani-infected peritoneal macrophages and BALB/c mice. We observed that F5 (15 µg/mL), F6 (10 µg/mL), and withaferin-A (1...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28534825/a-novel-combination-of-withaferin-a-and-sulforaphane-inhibits-epigenetic-machinery-cellular-viability-and-induces-apoptosis-of-breast-cancer-cells
#11
Kendra J Royston, Neha Udayakumar, Kayla Lewis, Trygve O Tollefsbol
With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28494348/withaferin-a-inhibits-prostate-carcinogenesis-in-a-pten-deficient-mouse-model-of-prostate-cancer
#12
Jim Moselhy, Suman Suman, Mohammed Alghamdi, Balaji Chandarasekharan, Trinath P Das, Alatassi Houda, Murali Ankem, Chendil Damodaran
We recently demonstrated that AKT activation plays a role in prostate cancer progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT inhibition and Par-4 induction suppressed prostate cancer progression in preclinical models. Here, we investigate the chemopreventive effect of the phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle over 45 weeks...
May 7, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28476645/withaferin-a-a-natural-compound-with-anti-tumor-activity-is-a-potent-inhibitor-of-transcription-factor-c-ebp%C3%AE
#13
Kim D Falkenberg, Anke Jakobs, Julian C Matern, Wolfgang Dörner, Sagar Uttarkar, Amke Trentmann, Simone Steinmann, Anna Coulibaly, Caroline Schomburg, Henning D Mootz, Thomas J Schmidt, Karl-Heinz Klempnauer
Recent work has shown that deregulation of the transcription factor Myb contributes to the development of leukemia and several other human cancers, making Myb and its cooperation partners attractive targets for drug development. By employing a myeloid Myb-reporter cell line we have identified Withaferin A (WFA), a natural compound that exhibits anti-tumor activities, as an inhibitor of Myb-dependent transcription. Analysis of the inhibitory mechanism of WFA showed that WFA is a significantly more potent inhibitor of C/EBPβ, a transcription factor cooperating with Myb in myeloid cells, than of Myb itself...
May 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#14
Katarzyna Szarc Vel Szic, Ken Declerck, René A J Crans, Jolien Diddens, David B Scherf, Clarissa Gerhäuser, Wim Vanden Berghe
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3)...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454064/withaferin-a-a-steroidal-lactone-encapsulated-mannose-decorated-liposomes-ameliorates-rheumatoid-arthritis-by-intriguing-the-macrophage-repolarization-in-adjuvant-induced-arthritic-rats
#15
Farhath Sultana, Manoj Kumar Neog, MahaboobKhan Rasool
In order to develop a better therapeutic approach for the treatment of rheumatoid arthritis (RA), withaferin-A; a steroidal lactone incorporated with mannosylated liposomes (ML-WA) was administered to adjuvant induced arthritic rats in intent to target the synovial macrophages. The confocal microscopy studies showed a successful internalization of ML-WA in the primarily isolated synovial macrophages. Consequently, targeting synovial macrophages via ML-WA reduced the oxidative stress (ROS and NO), and paw edema, however, a progressive gain in the body weight was observed in AIA rats...
April 23, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28445002/glucose-metabolism-targeted-therapy-and-withaferin-a-are-effective-for-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-induced-drug-tolerant-persisters
#16
Kei Kunimasa, Tatsuya Nagano, Yohei Shimono, Ryota Dokuni, Tatsunori Kiriu, Shuntaro Tokunaga, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Kazuyuki Kobayashi, Miyako Satouchi, Yoshihiro Nishimura
In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug-tolerant persisters (DTPs) substantially limits the overall therapeutic benefit. However, little is known about the roles of DTPs in drug resistance. In this study, we investigated the features of epidermal growth factor receptor-tyrosine kinase inhibitor-induced DTPs and explored a new treatment strategy to overcome the emergence of these DTPs. We used two EGFR-mutated lung adenocarcinoma cell lines, PC9 and II-18. They were treated with 2 μM gefitinib for 6, 12, or 24 days or 6 months...
July 2017: Cancer Science
https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#17
Yue Yu, Shashank P Katiyar, Durai Sundar, Zeenia Kaul, Eijiro Miyako, Zhenya Zhang, Sunil C Kaul, Roger R Reddel, Renu Wadhwa
Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers)...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28407087/rp-hplc-separation-of-isomeric-withanolides-method-development-validation-and-application-to-in-situ-rat-permeability-determination
#18
Mohd Yaseen Malik, Isha Taneja, Kanumuri Siva Rama Raju, Jiaur Rahaman Gayen, Sheelendra Pratap Singh, Neelam S Sangwand, Muhammad Wahajuddin
Withanolides are the group of active chemical constituents of Withania somnifera (L.) Dunal. Withaferin A, withanolide A and withanone presents three of the biologically most active constituents of this herb. These steroidal lactones are isomers of each other and thus, pose significant difficulty in their separation. In present study, a simple, specific and reliable RP-HPLC method has been developed and validated for their separation and simultaneous quantification. Separation was carried out on Lichrocart Purospher STAR RP-18e column (250 × 4...
April 12, 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/28387888/withaferin-a-induces-apoptosis-in-osteosarcoma-u2os-cell-line-via-generation-of-ros-and-disruption-of-mitochondrial-membrane-potential
#19
A-X Li, M Sun, X Li
OBJECTIVE: Withaferin-A (WF-A) is a well-known dietary compound isolated from Withania somnifera. It has marked pharmacological potential and has been shown to exhibit antiproliferative activity against several types of cancerous cells. Currently, the main focus of anti-cancer therapeutic development is to identify apoptosis-inducing drug-like molecules. Osteosarcoma is a rare type of bone cancer affecting humans. The objective of the present study was therefore to evaluate the antitumor potential of WF-A against several osteosarcoma cell lines...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28371543/upregulation-of-matrix-metalloproteinase-triggers-transdifferentiation-of-retinal-pigmented-epithelial-cells-in-xenopus-laevis-a-link-between-inflammatory-response-and-regeneration
#20
Hanako Naitoh, Yukari Suganuma, Yoko Ueda, Takahiko Sato, Yosuke Hiramuki, Atsuko Fujisawa-Sehara, Shigeru Taketani, Masasuke Araki
In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, we examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid...
April 2, 2017: Developmental Neurobiology
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