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Withaferin A

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https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
March 15, 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
#8
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 7, 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
#9
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
#10
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...
February 17, 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
#11
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
#12
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
https://www.readbyqxmd.com/read/28162105/molecular-insights-into-cancer-therapeutic-effects-of-the-dietary-medicinal-phytochemical-withaferin-a
#13
Chandra Sekhar Chirumamilla, Claudina Pérez-Novo, Xaveer Van Ostade, Wim Vanden Berghe
Despite the worldwide research efforts to combat cancer, it remains a leading cause of death. Although various specific kinase inhibitors already have been approved for clinical cancer treatment, occurrence of intrinsic or acquired resistance and intermittent response over longer periods limits long-term success of single kinase-targeted therapies. In this respect, there is a renewed interest in polypharmaceutical natural compounds, which simultaneously target various hyperactivated kinases involved in tumour-inflammation, angiogenesis, cell survival, proliferation, metastasis and angiogenesis...
February 6, 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28159699/drugs-targeting-intermediate-filaments-can-improve-neurosupportive-properties-of-astrocytes
#14
Yolanda de Pablo, Meng Chen, Elin Möllerström, Marcela Pekna, Milos Pekny
In response to central nervous system (CNS) injury, astrocytes upregulate intermediate filament (nanofilament) proteins GFAP and vimentin. Whereas the intermediate filament upregulation in astrocytes is important for neuroprotection in the acute phase of injury, in some contexts it might inhibit some of the regenerative processes later on. Thus, timely modulation of the astrocyte intermediate filaments was proposed as a strategy to promote brain repair. We used clomipramine, epoxomicin and withaferin A, drugs reported to decrease the expression of GFAP, and assessed their effect on neurosupportive properties and resilience of astrocytes to oxygen and glucose deprivation (OGD)...
January 31, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28040797/disease-subtype-independent-biomarkers-of-breast-cancer-chemoprevention-by-the-ayurvedic-medicine-phytochemical-withaferin-a
#15
Suman K Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Eun-Ryeong Hahm, Yongli Shuai, Ruchi Roy, Subrata K Pore, Krishna B Singh, Susan M Christner, Jan H Beumer, Nancy E Davidson, Shivendra V Singh
BACKGROUND: A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action. METHODS: Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group)...
June 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27942003/biochemical-and-cellular-determinants-of-renal-glomerular-elasticity
#16
Addie E Embry, Hamid Mohammadi, Xinying Niu, Liping Liu, Borren Moe, William A Miller-Little, Christopher Y Lu, Leslie A Bruggeman, Christopher A McCulloch, Paul A Janmey, R Tyler Miller
The elastic properties of renal glomeruli and their capillaries permit them to maintain structural integrity in the presence of variable hemodynamic forces. Measured by micro-indentation, glomeruli have an elastic modulus (E, Young's modulus) of 2.1 kPa, and estimates from glomerular perfusion studies suggest that the E of glomeruli is between 2 and 4 kPa. F-actin depolymerization by latrunculin, inhibition of acto-myosin contractility by blebbistatin, reduction in ATP synthesis, and reduction of the affinity of adhesion proteins by EDTA reduced the glomerular E to 1...
2016: PloS One
https://www.readbyqxmd.com/read/27936030/novel-methods-to-generate-active-ingredients-enriched-ashwagandha-leaves-and-extracts
#17
Sunil C Kaul, Yoshiyuki Ishida, Kazuya Tamura, Teruo Wada, Tomoko Iitsuka, Sukant Garg, Mijung Kim, Ran Gao, Shoichi Nakai, Youji Okamoto, Keiji Terao, Renu Wadhwa
Ashwagandha (Withania somnifera) is an Ayurvedic herb commonly used in world-renowned traditional Indian home medicine system. Roots of Ashwagandha have been traditionally known to possess a variety of therapeutic and health promoting potentials that have not been sufficiently supported by laboratory studies. Nevertheless, most, if not all, of the preventive and therapeutic potentials have been assigned to its bioactive components, steroidal alkaloids and lactones. In contrast to the traditional use of roots, we have been exploring bioactivities in leaves of Ashwagandha...
2016: PloS One
https://www.readbyqxmd.com/read/27915154/lipopolysaccharides-stimulated-macrophage-products-enhance-withaferin-a-induced-apoptosis-via-activation-of-caspases-and-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-human-cancer-cells
#18
Liang Piao, Zhao Canguo, Lu Wenjie, Cheng Xiaoli, Shi Wenli, Lu Li
Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2)...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27867044/mitochondrial-dysfunction-in-cancer-chemoprevention-by-phytochemicals-from-dietary-and-medicinal-plants
#19
REVIEW
Anuradha Sehrawat, Ruchi Roy, Subrata K Pore, Eun-Ryeong Hahm, Suman K Samanta, Krishna B Singh, Su-Hyeong Kim, Kamayani Singh, Shivendra V Singh
Cancer chemoprevention, a scientific term coined by Dr. Sporn in the late seventies, implies use of natural or synthetic chemicals to block, delay or reverse carcinogenesis. Phytochemicals derived from edible and medicinal plants have been studied rather extensively for cancer chemoprevention using preclinical models in the past few decades. Nevertheless, some of these agents (e.g., isothiocyanates from cruciferous vegetables like broccoli and watercress) have already entered into clinical investigations. Examples of widely studied and highly promising phytochemicals from edible and medicinal plants include cruciferous vegetable constituents (phenethyl isothiocyanate, benzyl isothiocyanate, and sulforaphane), withaferin A (WA) derived from a medicinal plant (Withania somnifera) used heavily in Asia, and an oriental medicine plant component honokiol (HNK)...
November 17, 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27859734/withanolides-against-tlr4-activated-innate-inflammatory-signalling-pathways-a-comparative-computational-and-experimental-study
#20
Preethi M Purushotham, Jin-Man Kim, Eun-Kyeong Jo, Kalaiselvi Senthil
Innate inflammations are dominant causes of poor health and high mortality. The pathogen-associated molecular pattern and lipopolysaccharide (LPS) are sensed by immune cells through activation of toll-like receptor 4 leading to mitogen-activated protein kinases (MAPKs) and NF-κB activations. Controlled MAPK and Nf-κB inhibitors have been proposed as potential antiinflammatory drugs. Withania somnifera is an important medicinal herb with known antiinflammatory activity. In this study, the selected Withania somnifera extracts and withanolides were analysed on LPS-induced macrophages comparatively...
January 2017: Phytotherapy Research: PTR
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