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Withaferin A

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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-targeting-therapy-and-withaferin-a-are-effective-for-egfr-tki-induced-drug-tolerant-persisters
#8
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 EGFR-TKI 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 month...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28365961/withaferin-a-induces-mitochondrial-dependent-apoptosis-in-non-small-cell-lung-cancer-cells-via-generation-of-reactive-oxygen-species
#13
Xi Liu, Lei Chen, Tao Liang, Xiao-Dong Tian, Yang Liu, Tao Zhang
PURPOSE: Withaferin A (WA) is a bioactive lactone, isolated from natural sources, mainly found in Withania somnifera, and was known to be highly effective against a variety of tumor cells both in vitro and in vivo. Accumulating experimental evidence suggests the involvement of reactive oxygen species (ROS) in WA-mediated cytotoxicity against cancer cells. Hence, the purpose of this study was to investigate the effect of WA in non-small cell lung cancer (NSCLC) cells and also the role of ROC in WA-mediated cytotoxicity...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28350459/stat3-inhibitory-activity-of-structurally-simplified-withaferin-a-analogues
#14
Teruyuki Tahara, Ursula Streit, Henry E Pelish, Matthew D Shair
Signal transducer and activator of transcription 3 (STAT3) is a component of the JAK/STAT pathway. Therapeutic inhibition of STAT3 has been of high interest, as its aberrant activation has been linked to cancer, inflammation, and other human diseases. The withanolide family natural product withaferin A (1) inhibits STAT3 activation. We designed, synthesized, and evaluated simplified withanolide analogues SLW1 (3) and SLW2 (4), and found that SLW1 retained the STAT3 inhibitory activity of withaferin A.
April 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28295751/the-role-of-plant-derived-products-in-pancreatitis-experimental-and-clinical-evidence
#15
REVIEW
Pratibha Anchi, Amit Khurana, Swarna Bale, Chandraiah Godugu
Pancreatitis is a gastrointestinal disease with a worldwide sharp surge during the past decade. Pancreatitis includes acute and chronic subtypes, which are graded based on the amount of pancreatic inflammation. Phytoconstituents represent a promising class of therapeutic agents with wide acceptability not only based on folk practices but sound presence of pharmacological and molecular evidences. Growing research evidence indicates that different molecular mechanisms are involved in their protective effect. Many phytoremedies have been tried for the treatment of pancreatic injuries and have shown success in preclinical animal models of pancreatitis...
April 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28282606/protection-against-cerebral-infarction-by-withaferin-a-involves-inhibition-of-neuronal-apoptosis-activation-of-pi3k-akt-signaling-pathway-and-reduced-intimal-hyperplasia-via-inhibition-of-vsmc-migration-and-matrix-metalloproteinases
#16
Qi-Zhi Zhang, Yu-Dong Guo, Hao-Mei Li, Rui-Zheng Wang, Shou-Gang Guo, Yi-Feng Du
PURPOSE: Stroke is a major public health concern with high rates of morbidity and mortality worldwide. Cerebral ischemia and infarction are commonly associated with stroke. Currently used medications, though effective, are also associated with adverse effects. Development of effective neuroprotective agents with fewer side effects would be of clinical value. We evaluated the effects of Withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera, on experimentally induced cerebral infarction...
March 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28257574/17%C3%AE-hydroxywithanolides-as-sensitizers-of-renal-carcinoma-cells-to-tumor-necrosis-factor-%C3%AE-related-apoptosis-inducing-ligand-trail-mediated-apoptosis-structure-activity-relationships
#17
Ya-Ming Xu, Alan D Brooks, E M Kithsiri Wijeratne, Curtis J Henrich, Poonam Tewary, Thomas J Sayers, A A Leslie Gunatilaka
Renal cell carcinoma (RCC) is a cancer with poor prognosis, and the 5-year survival rate of patients with metastatic RCC is 5-10%. Consequently, treatment of metastatic RCC represents an unmet clinical need. Screening of a 50 000-member library of natural and synthetic compounds for sensitizers of RCC cells to TRAIL-mediated apoptosis led to identification of the 17β-hydroxywithanolide (17-BHW), withanolide E (1), as a promising lead. To explore structure-activity relationships, we obtained natural and semisynthetic withanolides 1, 2a, 2c, and 3-36 and compared their ability to sensitize TRAIL-mediated apoptosis in a panel of renal carcinoma cells...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28249222/comparative-study-of-withanolide-production-and-the-related-transcriptional-responses-of-biosynthetic-genes-in-fungi-elicited-cell-suspension-culture-of-withania-somnifera-in-shake-flask-and-bioreactor
#18
COMPARATIVE STUDY
Seema Ahlawat, Parul Saxena, Athar Ali, Shazia Khan, Malik Z Abdin
Ashwagandha (Withania somnifera) is one of the most reputed medicinal plants in the traditional medicinal system. In this study, cell suspension culture of W. somnifera was elicited with cell homogenates of fungi (A. alternata, F. solani, V. dahliae and P. indica) in shake flask and the major withanolides like withanolide A, withaferin A and withanone were analysed. Simultaneously expression levels of key pathway genes from withanolides biosynthetic pathways were also checked via quantitative PCR in shake flask as well as in bioreactor...
May 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28228044/withaferin-a-protects-against-spinal-cord-injury-by-inhibiting-apoptosis-and-inflammation-in-mice
#19
Xianlei Yan, Guangxiang Huang, Quan Liu, Jiemin Zheng, Hongmou Chen, Qidan Huang, Jiakang Chen, Heqing Huang
CONTEXT: Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection. OBJECTIVE: We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI). MATERIALS AND METHODS: BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#20
Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo A Ferrando
The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
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