Diallyl Disulfide (DADS) Induces Apoptosis in Human Cervical

Total Page:16

File Type:pdf, Size:1020Kb

Diallyl Disulfide (DADS) Induces Apoptosis in Human Cervical ANTICANCER RESEARCH 28 : 2791-2800 (2008) Diallyl Disulfide (DADS) Induces Apoptosis in Human Cervical Cancer Ca Ski Cells via Reactive Oxygen Species and Ca 2+ -dependent Mitochondria-dependent Pathway YUH-TZY LIN 1, JAI-SING YANG 2, SHUW-YUAN LIN 3, TZU-WEI TAN 2, CHIN-CHIN HO 4, TE-CHUN HSIA 5, TSAN-HUNG CHIU 6, CHUN-SHU YU 7, HSU-FENG LU 8, YUEH-SHAN WENG 9 and JING-GUNG CHUNG 9,10 1Department of Nursing and Management, Jen-Teh Junior College of Medicine, Miaoli, Taiwan; Departments of 2Pharmacology and 9Biological Science and Technology, 7School of Pharmacology, China Medical University, Taichung, Taiwan; Department of 5Internal Medicine and 6OBS/GYN, China Medical University Hospital, Taichung, Taiwan; 3Department of Food and Nutrition, Hung-Kuang University, Sha Lu, Taichung Hsien 433, Taiwan 4Department of Nurs ing , Central Taiwan University of Science and Technology, Buzih District, Taiwan; 8Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan; 10 Department of Biotechnology, Asia University, Wufeng, Taichung County 41354, Taiwan, R.O.C. Abstract. The mechanisms of apoptosis induced by diallyl naturally in garlic, is known to inhibit the growth of disulfide (DADS) were explored in human cervical cancer Ca canine mammary neoplastic CMT-13 cells (1), the Ski cells. Flow cytometric analysis, DNA gel electrophoresis promotion phase of DMBA-induced skin tumors in mice and DAPI staining demonstrated that DADS induced apoptosis (2) and also to inhibit rat and human CYP2E1 and rat in Ca Ski cells. DADS induced apoptosis through the CYP2A3 expressions (3). DADS induced apoptosis in production of reactive oxygen species and Ca 2+ , and induced HepG2 hepatoma (4) and neuroblastoma cells (5) and it abrogation of mitochondrial membrane potential (Δψm) and was suggested as an antiproliferative agent in cancer cleavage of Bid protein (t-Bid). DADS increased the levels of therapy based on a pivotal role for oxidative stress (5). p53, p21 and Bax, but caused a decrease in the level of Bcl-2. DADS affects histone acetylation and this may be DADS also promoted the activities of caspase-3 leading to associated with its protective properties in colon DNA fragmentation, thus indicating that DADS-induced carcinogenesis (6). In our previous studies, we apoptosis is caspase-3 dependent. In addition, DADS induced demonstrated that DADS affects NAT activity and gene an increase in the level of cytochrome c in the cytoplasm, which expression in human cancer cell lines (7-9). Recently, we was released from mitochondria. BAPTA attenuated the Δψm also found that DADS induced signal transducer and abrogation and significantly diminished the occurrence of activator of transcription 1 (STAT 1) expression in human DADS-induced apoptosis in Ca Ski cells. In conclusion, DADS- colon cancer COLO 205 cells (10). induced apoptosis occurs via production of ROS and caspase- Apoptosis, a programmed cell death, occurs under a 3 and a mitochondria-dependent pathway in Ca Ski cells. variety of physiological and pathological conditions that control the development and homeostasis of multicellular Garlic ( Allium sativum L.) is well known for its organisms (11). The induction of apoptosis was recognized chemopreventive potential against cancer, especially colon to be the best strategy for agents to kill cancer cells. The cancer. Diallyl disulfide (DADS), a compound found major apoptotic pathways can be divided into caspase- and mitochondria-dependent pathways. Caspase activation is generally considered to be a key hallmark of apoptosis. Although DADS has been demonstrated to induce apoptosis Correspondence to: Jing-Gung Chung, Ph.D., Department of in colon cancer cells through the ROS-dependent Biological Science and Technology, China Medical University, No 91, mitochondrial death pathway, there is no available Hsueh-Shih Road, Taichung 404, Taiwan, R.O.C. Tel: +886 422053366, Fax: +886 422053764, e-mail: jgchung@ mail.cmu.edu.tw information on the effects of DADS in human cervical cancer Ca Ski cells. Therefore, in this study we focused on 2+ Key Words: DADS, apoptosis, caspase-3, cytochrome c, the molecular mechanism and the role of ROS and Ca on mitochondrial membrane potential (Δψm). the induction of apoptosis by DADS in Ca Ski cells. 0250-7005/2008 $2.00+.40 2791 ANTICANCER RESEARCH 28 : 2791-2800 (2008) Materials and Methods Caspase-3 activity determination in Ca Ski cells treated with or without DADS. Approximately 2×10 5 Ca Ski cells/well in 12-well plates with 25 μM DADS were incubat ed for 0, 6, 12, 24 and 48 h. Chemicals and reagents. Diallyl disulfide (DADS) was purchased Cells were harvested before adding 50 μl of 10 μM substrate solution from Fluka Chemika Co. (Bucha, Switzerland). Dimethyl sulfoxide to the cell pellet (1×10 5 cells per sample) and cells were incubated (DMSO), propidium iodide (PI), RNase, trypan blue, Tris-HCl and at 37˚C for 60 min then washed once with 1 ml of ice-cold PBS and Triton X-100 were obtained from Sigma Chemical Co. (St. Louis, re-suspended in 1 ml fresh PBS. Cells were analyzed with a flow MO, USA). BAPTA and potassium phosphates were obtained from cytometer (Becton-Dickinson) equipped with an argon ion laser at Merck Co. (Darmstadt, Germany). Fetal bovine serum (FBS), 488 nm. Caspase-3 activity was determined and analyzed (17, 18) glutamine, penicillin-streptomycin, trypsin-EDTA and RPMI-1640 according to the manufacturer’s instructions. were obtained from Gibco BRL (Grand Island, NY, USA). Caspase-3 activity assay kit was bought from OncoImmunin, Inc (Gaithersburg, Detection of reactive oxygen species (ROS) in Ca Ski cells after MD, USA). treatment with DADS. Approximately 2×10 5 Ca Ski cells/well in 12-well plates were treated with 25 μM DADS for 0, 2, 4 and 5 h. Human cervical epidermoid carcinoma Ca Ski cells. Ca Ski cells were The cells were harvested and washed twice, re-suspended in 500 μl obtained from the Food Industry Research and Development Institute of 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) (10 μM) (Hsinchu, Taiwan, ROC). The cells were placed into 75 cm 3 tissue and incubated at 37˚C for 30 min, then analyzed to detect the culture flasks and grown at 37˚C under a humidified 5% CO and 95% 2 changes of ROS by flow cytometry (17, 18). air at 1 Atm in RPMI-1640 medium supplemented with 10% FBS, 1% penicillin-streptomycin (10,000 U/ml penicillin and 10 mg/ml Detection of the levels of cytoplasmic Ca 2+ in DADS-treated Ca Ski streptomycin) and 1% L-glutamine. Cells were cultured for several cells. Approximately 2×10 5 Ca Ski cells/well in 12-well plates were generations and the viability of each generation was checked (12). treated with 25 μM DADS for 0, 0.25, 1, 3, 4, 6 and 8 h. The cells were harvested and washed twice, re-suspended in Indo 1/AM Morphological changes and cell viability of Ca Ski cells treated with (3 μg/ml), incubated at 37˚C for 30 min, then analyzed to detect the or without DADS. The Ca Ski cells were plated in 12-well plates at changes of cytoplasmic Ca 2+ levels using flow cytometry (17, 18). a density of 2×10 5 cells/well and grown for 24 h. DADS was individually added to cells at a final concentration of 0, 10, 25, 50, Detection of mitochondrial membrane potential (Δψm) in Ca Ski 75 and 100 μM, while DMSO (solvent) alone was added to the cells after treatment with DADS. Approximately 2×10 5 Ca Ski control group. The cells were grown at 37˚C, 5% CO and 95% air 2 cells/well in 12-well plates were treated with 25 μM DADS for 0, for different periods of time. For morphological changes, cells were 0.25, 1, 6 and 24 h. The cells were harvested and washed twice, re- examined and photographed under phase-contrast light microscopy. suspended in 500 μl of DiOC (4 μmol/l) and incubated at 37˚C for For cell viability, propidium iodi de (PI) stain was used and a flow 6 30 min before being analyzed to detect the changes of mitochondrial cytometric assay was carried out as described elsewhere (12, 13). membrane potential (Δψm) using flow cytometry (17, 18). Flow cytometric analysis for apoptosis. Approximately 5×10 5 Detection of the levels of cytoplasmic Ca 2+ and Δψm in Ca Ski cells cells/well Ca Ski in 6-well plates were incubated with 25 μM DADS pre-treated with BAPTA then treated with DADS. Approximately for 0, 6, 12, 24, 48 and 72 hours. The isolated cells were fixed gently 2×10 5 Ca Ski cells/well in 12-well plates were pre-treated with (drop by drop) by putting 70% ethanol (in PBS) in ice overnight and BAPTA before the addition of 25 μM DADS for 24 hours. The cells were then resuspended in phosphate-buffered saline (PBS) containing were harvested and washed twice, once for apoptosis analysis and 40 μg/m l PI, 0.1 mg/ml RNase (Sigma) and 0.1% Triton X-100 in a the other for re-suspension in Indo 1/AM (3 μg/ml) or DiOC dark room. After 30 minutes at 37˚C, the cells were analyzed with a 6 (4 μmol/L) before being incubated at 37˚C for 30 min and then flow cytometer (Becton Dickinson FACS Calibur, San Jose, CA, analyzed by flow cytometry. USA) equipped with an argon laser at 488 nm. The cell cycle distribution was determined and analyzed (13, 14). Western blotting to examine the effect of DADS on p53, p21, Bax, Bcl-2, caspase-3 AIF, MMP-1, -7 and -9, Bid, tBid and cytochrome DAPI staining for the effects of DADS on apoptosis in Ca Ski cells.
Recommended publications
  • Food Compounds Activating Thermosensitive TRP Channels in Asian Herbal and Medicinal Foods
    J Nutr Sci Vitaminol, 61, S86–S88, 2015 Food Compounds Activating Thermosensitive TRP Channels in Asian Herbal and Medicinal Foods Tatsuo WATANABE and Yuko TERADA School of Food and Nutritional Sciences, University of Shizuoka, 52–1 Yada, Suruga-ku, Shizuoka 422–8526, Japan Summary There are several thermosensitive transient receptor potential (TRP) ion chan- nels including capsaicin receptor, TRPV1. Food components activating TRPV1 inhibit body fat deposition through sympathetic nerve stimulation. TRPA1 is another pungency sensor for pungent compounds and is mainly coexpressed with TRPV1 in sensory nerve endings. Therefore, TRPA1 activation is expected to have an anti-obesity effect similar to TRPV1 activation. We have searched for agonists for TRPV1 and TRPA1 in vitro from Asian spices by the use of TRPV1- and TRPA1-expressing cells. Further, we performed food component addition tests to high-fat and high-sucrose diets in mice. We found capsiate, capsiconiate, capsainol from hot and sweet peppers, several piperine analogs from black pepper, gingeriols and shogaols from ginger, and sanshools and hydroxysanshools from sansho (Japanese pep- per) to be TRPV1 agonists. We also identified several sulfides from garlic and durian, hydroxy fatty acids from royal jelly, miogadial and miogatrial from mioga (Zingiber mioga), piper- ine analogs from black pepper, and acetoxychavicol acetate (ACA) from galangal (Alpinia galanga) as TRPA1 agonists. Piperine addition to diets diminished visceral fats and increased the uncoupling protein 1 (UCP1) in interscapular brown adipose tissue (IBAT), and black pepper extract showed stronger effects than piperine. Cinnamaldehyde and ACA as TRPA1 agonists inhibited fat deposition and increased UCP1. We found that several agonists of TRPV1 and TRPA1 and some agonists of TRPV1 and TRPA1 inhibit visceral fat deposition in mice.
    [Show full text]
  • Note: the Letters 'F' and 'T' Following the Locators Refers to Figures and Tables
    Index Note: The letters ‘f’ and ‘t’ following the locators refers to figures and tables cited in the text. A Acyl-lipid desaturas, 455 AA, see Arachidonic acid (AA) Adenophostin A, 71, 72t aa, see Amino acid (aa) Adenosine 5-diphosphoribose, 65, 789 AACOCF3, see Arachidonyl trifluoromethyl Adlea, 651 ketone (AACOCF3) ADP, 4t, 10, 155, 597, 598f, 599, 602, 669, α1A-adrenoceptor antagonist prazosin, 711t, 814–815, 890 553 ADPKD, see Autosomal dominant polycystic aa 723–928 fragment, 19 kidney disease (ADPKD) aa 839–873 fragment, 17, 19 ADPKD-causing mutations Aβ, see Amyloid β-peptide (Aβ) PKD1 ABC protein, see ATP-binding cassette protein L4224P, 17 (ABC transporter) R4227X, 17 Abeele, F. V., 715 TRPP2 Abbott Laboratories, 645 E837X, 17 ACA, see N-(p-amylcinnamoyl)anthranilic R742X, 17 acid (ACA) R807X, 17 Acetaldehyde, 68t, 69 R872X, 17 Acetic acid-induced nociceptive response, ADPR, see ADP-ribose (ADPR) 50 ADP-ribose (ADPR), 99, 112–113, 113f, Acetylcholine-secreting sympathetic neuron, 380–382, 464, 534–536, 535f, 179 537f, 538, 711t, 712–713, Acetylsalicylic acid, 49t, 55 717, 770, 784, 789, 816–820, Acrolein, 67t, 69, 867, 971–972 885 Acrosome reaction, 125, 130, 301, 325, β-Adrenergic agonists, 740 578, 881–882, 885, 888–889, α2 Adrenoreceptor, 49t, 55, 188 891–895 Adult polycystic kidney disease (ADPKD), Actinopterigy, 223 1023 Activation gate, 485–486 Aframomum daniellii (aframodial), 46t, 52 Leu681, amino acid residue, 485–486 Aframomum melegueta (Melegueta pepper), Tyr671, ion pathway, 486 45t, 51, 70 Acute myeloid leukaemia and myelodysplastic Agelenopsis aperta (American funnel web syndrome (AML/MDS), 949 spider), 48t, 54 Acylated phloroglucinol hyperforin, 71 Agonist-dependent vasorelaxation, 378 Acylation, 96 Ahern, G.
    [Show full text]
  • Computational Modeling of Lysine Post-Translational Modification: an Overview Md
    c and S eti ys h te nt m y s S B Hasan MM et al., Curr Synthetic Sys Biol 2018, 6:1 t i n o e l Current Synthetic and o r r g DOI: 10.4172/2332-0737.1000137 u y C ISSN: 2332-0737 Systems Biology CommentaryResearch Article OpenOpen Access Access Computational Modeling of Lysine Post-Translational Modification: An Overview Md. Mehedi Hasan 1*, Mst. Shamima Khatun2, and Hiroyuki Kurata1,3 1Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan 2Department of Statistics, Laboratory of Bioinformatics, Rajshahi University-6205, Bangladesh 3Biomedical Informatics R&D Center, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan Commentary hot spot for PTMs, and a number of protein lysine modifications could occur in both histone and non-histone proteins [11,12]. For instance, Living organisms have a magnificent ordered and complex lysine methylation in non-histone proteins can regulate the protein structure. In regulating the cellular functions, post-translational activity and protein structure stability [13]. In 2004, the Nobel Prize in modifications (PTMs) are critical molecular measures. They alter Chemistry was awarded jointly to Aaron Ciechanover, Avram Hershko protein conformation, modulating their activity, stability and and Irwin Rose for the discovery of lysine ubiquitin-mediated protein localization. Up to date, more than 300 types of PTMs are experimentally degradation [14]. discovered in vivo and in vitro pathways [1,2]. Major and common PTMs are methylation, ubiquitination, succinylation, phosphorylation, Moreover, in biological process, lysine can be modified by the glycosylation, acetylation, and sumoylation.
    [Show full text]
  • Trpa1) Activity by Cdk5
    MODULATION OF TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY A, MEMBER 1 (TRPA1) ACTIVITY BY CDK5 A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Michael A. Sulak December 2011 Dissertation written by Michael A. Sulak B.S., Cleveland State University, 2002 Ph.D., Kent State University, 2011 Approved by _________________, Chair, Doctoral Dissertation Committee Dr. Derek S. Damron _________________, Member, Doctoral Dissertation Committee Dr. Robert V. Dorman _________________, Member, Doctoral Dissertation Committee Dr. Ernest J. Freeman _________________, Member, Doctoral Dissertation Committee Dr. Ian N. Bratz _________________, Graduate Faculty Representative Dr. Bansidhar Datta Accepted by _________________, Director, School of Biomedical Sciences Dr. Robert V. Dorman _________________, Dean, College of Arts and Sciences Dr. John R. D. Stalvey ii TABLE OF CONTENTS LIST OF FIGURES ............................................................................................... iv LIST OF TABLES ............................................................................................... vi DEDICATION ...................................................................................................... vii ACKNOWLEDGEMENTS .................................................................................. viii CHAPTER 1: Introduction .................................................................................. 1 Hypothesis and Project Rationale
    [Show full text]
  • Garlic and Gaseous Mediators
    TIPS 1521 No. of Pages 11 Review Garlic and Gaseous Mediators Peter Rose,1,2,* Philip Keith Moore,3 and Yi-Zhun Zhu2 Garlic (Allium sativum) and allied plant species are rich sources of sulfur Highlights compounds. Major roles for garlic and its sulfur constituents include the Garlic has been used for centuries to regulation of vascular homeostasis and the control of metabolic systems linked treat human diseases. to nutrient metabolism. Recent studies have indicated that some of these sulfur Sulfur compounds present in the compounds, such as diallyl trisulfide (DATS), alter the levels of gaseous sig- edible parts of garlic can alter the levels of gaseous signalling molecules like nalling molecules including nitric oxide (NO), hydrogen sulfide (H2S), and per- NO, CO, and H2S in mammalian cells haps carbon monoxide (CO) in mammalian tissues. These gases are important and tissues. in cellular processes associated with the cardiovascular system, inflammation, Some of garlic’s sulfur compounds and neurological functions. Importantly, these studies build on the known have been found to act as natural biological effects of garlic and associated sulfur constituents. This review H2S donor molecules. highlights our current understanding of the health benefits attributed to edible plants like garlic. Garlic and Its Many Roles Garlic (Allium sativum) has been used in the treatment and prevention of a wide variety of ailments for centuries [1]. The best known of these are the use of garlic as a ‘blood-thinning’ agent in China and India [2], as a treatment for asthma, for bacterial infections such as leprosy, and for heart disorders by the Egyptians [3].
    [Show full text]
  • Role of Hydrogen Sulfide Donors in Cancer Development and Progression
    Int. J. Biol. Sci. 2021, Vol. 17 73 Ivyspring International Publisher International Journal of Biological Sciences 2021; 17(1): 73-88. doi: 10.7150/ijbs.47850 Review Role of hydrogen sulfide donors in cancer development and progression Ebenezeri Erasto Ngowi1,3,4, Attia Afzal1,5, Muhammad Sarfraz1,4,5, Saadullah Khattak1,6, Shams Uz Zaman1,6, Nazeer Hussain Khan1,6, Tao Li1, Qi-Ying Jiang1, Xin Zhang7, Shao-Feng Duan1,7,, Xin-Ying Ji1,8,, Dong-Dong Wu1,2, 1. Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan 475004, China 2. School of Stomatology, Henan University, Kaifeng, Henan 475004, China 3. Department of Biological Sciences, Faculty of Science, Dar es Salaam University College of Education, Dar es Salaam 2329, Tanzania 4. Kaifeng Municipal Key Laboratory of Cell Signal Transduction, Henan Provincial Engineering Centre for Tumor Molecular Medicine, Henan University, Kaifeng, Henan 475004, China 5. Faculty of Pharmacy, The University of Lahore, Lahore, Punjab 56400, Pakistan 6. School of Life Sciences, Henan University, Kaifeng, Henan 475004, China 7. Institute for Innovative Drug Design and Evaluation, School of Pharmacy, Henan University, Kaifeng, Henan 475004, China 8. Kaifeng Key Laboratory of Infection and Biological Safety, School of Basic Medical Sciences, Henan University, Kaifeng, Henan 475004, China Corresponding authors: [email protected] (D.-D. W.); [email protected] (S.-F. D.); [email protected] (X.-Y. J.); +86 371 23880525 (D.-D. W.), +86 371 23880680 (S.-F. D.), +86 371 23880585 (X.-Y. J.). © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
    [Show full text]
  • P53 Acetylation: Regulation and Consequences
    Cancers 2015, 7, 30-69; doi:10.3390/cancers7010030 OPEN ACCESS cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review p53 Acetylation: Regulation and Consequences Sara M. Reed 1,2 and Dawn E. Quelle 1,2,3,* 1 Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; E-Mail: [email protected] 2 Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA 3 Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-319-353-5749; Fax: +1-319-335-8930. Academic Editor: Rebecca S. Hartley Received: 18 March 2014 / Accepted: 12 December 2014 / Published: 23 December 2014 Abstract: Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression.
    [Show full text]
  • Subject Index
    Subject Index Boldface denotes illustration or figure N-acetyl-S-allylcysteine (also called in oil-macerated garlic supplements, 239 allyl mercapturic acid) platelet aggregation effect of, 270, 272 in urine following consumption of stability toward heat, 191 garlic, 81 stereochemistry of addition reactions at C=C bond, 190 carbophilic, 196, 197, 205, 223 at sulfoxide sulfur, 190, 191 thiophilic, 205 A. keratitis (Acanthamoeba keratitis), garlic ajoene (AllS(O)CH2CH=CHSSAll) and, 253 antibiotic activity, 246, 399–401 alembic, 62, 64 B. subtilis, 399 S-alk(en)ylcysteine sulfoxides, 141, 142 E. coli, 399 in alliums, amounts and kinds, 396–398 H. pylori, 249, 399 biosynthesis, 168–171 K. pneumoniae, 399 in Brassica oleracea, 170 M. phlei, 400 derivatization of, 144 M. smegmatis, 400 γ-glutamyl derivatives of, 165-171 P. aeruginosa, 399 in Leucocoryne, 172 S. aureus, 400 in mushrooms, 172 anticancer activity in Petiveria alliacea, 172 basal cell carcinoma treatment, 258, in Scorodocarpus borneensis (wood 259, 260 garlic), 172 leukemia treatment, 262 in Tulbaghia violacea (society garlic), 172 mechanism of, 262 allelopathy, 26, 299, 300 antifungal activity, 248, 319, 400, 401 allicin (AllS(O)SAll) antithrombotic activity, 190, 270, 272 ajoene from, 172 antiviral activity, 253, 254 allergy to, 288 cholesterol lowering and, 269 analysis of, discovery of, 190 by DART, 158, 159 formation from allicin, 70, 172, 191, 192 by LC-MS, from garlic and ramp, monomethyl and dimethyl analogs, 193 145–147 name, derivation of, 190 by SFC, from garlic, 165 434 Subject Index 435 antibiotic activity of, 69, 72, 244, 318, thioacrolein from, 155 319, 399–401 3-vinyl-4H-1,2-dithiin and 2-vinyl- E.
    [Show full text]
  • Garlic, the Spice of Life-(Part –I) Kishu Tripathi Surya College of Pharmacy, Lucknow
    Asian J. Research Chem. 2(1): Jan.-March, 2009 , ISSN 0974-4169 www.ajrconline.org REVIEW ARTICLE A Review –Garlic, the Spice of Life-(Part –I) Kishu Tripathi Surya College of Pharmacy, Lucknow ABSTRACT Garlic [Allium sativum] is among the oldest of all cultivated plants. It has been used as a medicinal agent for thousands of years. It is a remarkable plant, which has multiple beneficial effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor activity etc KEY WORDS Garlic,Allium INTRODUCTION: Garlic has played an important dietary and medicinal role Preparations of garlic are available as tablets, capsules, throughout the history of mankind. Garlic is a nature’s boon to syrup, tinctures and oil. In ointment form, garlic has been mankind. For over 5000 years garlic has been consumed both used externally for treatment of ring worm; boiled with as food and used for medicine by ancient scholars. Garlic, vinegar and sugar for treatment of asthma; made into an Allium sativum L. is a member of the Alliaceae family, has infusion for treatment of epilepsy; pounded with honey for been widely recognized as a valuable spice and a popular use against rheumatism; and mixed with milk for use as a remedy for various ailments and physiological disorders. The vermifuge. Garlic is commonly used in Europe and Asia for name garlic may have originated from the Celtic word 'all' medicinal benefits in healing wounds, etc.In Germany, sale meaning pungent. As one of the earliest cultivated plants, of garlic preparations competes with sales of leading garlic is mentioned in the Bible and in the literature of Ancient drugs.Garlic produces a variety of volatile sulfur-based Israel (The Talmud), Egypt (Codex Ebers) and India (Vedas compounds which are effective as insect repellents and and Purans, Charak Sanghita).Chinese strongly believe that insecticides.
    [Show full text]
  • Protein Acetylation at the Interface of Genetics, Epigenetics and Environment in Cancer
    H OH metabolites OH Review Protein Acetylation at the Interface of Genetics, Epigenetics and Environment in Cancer Mio Harachi 1, Kenta Masui 1,* , Webster K. Cavenee 2, Paul S. Mischel 3 and Noriyuki Shibata 1 1 Department of Pathology, Division of Pathological Neuroscience, Tokyo Women’s Medical University, Tokyo 162-8666, Japan; [email protected] (M.H.); [email protected] (N.S.) 2 Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA; [email protected] 3 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; [email protected] * Correspondence: [email protected]; Tel.: +81-3-3353-8111; Fax: +81-3-5269-7408 Abstract: Metabolic reprogramming is an emerging hallmark of cancer and is driven by abnormalities of oncogenes and tumor suppressors. Accelerated metabolism causes cancer cell aggression through the dysregulation of rate-limiting metabolic enzymes as well as by facilitating the production of intermediary metabolites. However, the mechanisms by which a shift in the metabolic landscape reshapes the intracellular signaling to promote the survival of cancer cells remain to be clarified. Recent high-resolution mass spectrometry-based proteomic analyses have spotlighted that, unex- pectedly, lysine residues of numerous cytosolic as well as nuclear proteins are acetylated and that this modification modulates protein activity, sublocalization and stability, with profound impact on cellular function. More importantly, cancer cells exploit acetylation as a post-translational protein for microenvironmental adaptation, nominating it as a means for dynamic modulation of the phenotypes of cancer cells at the interface between genetics and environments.
    [Show full text]
  • Control of Smad7 Stability by Competition Between Acetylation and Ubiquitination
    Molecular Cell, Vol. 10, 483–493, September, 2002, Copyright 2002 by Cell Press Control of Smad7 Stability by Competition between Acetylation and Ubiquitination Eva Gro¨ nroos, Ulf Hellman, Carl-Henrik Heldin, 1998), where it binds the receptors and inhibits further and Johan Ericsson1 signaling by at least two different mechanisms. First, Ludwig Institute for Cancer Research Smad7 is able to interfere with TGF␤ signaling by Box 595 blocking the interactions between the R-Smads and the Husargatan 3 activated receptors (Hayashi et al., 1997; Nakao et al., S-751 24 Uppsala 1997). Second, Smad7 interacts with the E3-ubiquitin Sweden ligases Smurf1 or Smurf2 in the nucleus; after TGF␤ stimulation, the Smad7-Smurf complex translocates from the nucleus to the plasma membrane, where Smurf Summary induces ubiquitination and degradation of the TGF␤ re- ceptors (Ebisawa et al., 2001; Kavsak et al., 2000). Smad proteins regulate gene expression in response Acetylation is a dynamic posttranslational modifica- to TGF␤ signaling. Here we present evidence that tion of lysine residues. Proteins with intrinsic histone Smad7 interacts with the transcriptional coactivator acetyltransferase (HAT) activity act as transcriptional p300, resulting in acetylation of Smad7 on two lysine coactivators by acetylating histones and thereby induce residues in its N terminus. Acetylation or mutation of an open chromatin conformation, which allows the tran- these lysine residues stabilizes Smad7 and protects scriptional machinery access to promoters (Roth et al., it from TGF␤-induced degradation. Furthermore, we 2001). The best characterized HATs are p300, CBP, and demonstrate that the acetylated residues in Smad7 P/CAF (Roth et al., 2001).
    [Show full text]
  • Acetylation Promotes Tyrrs Nuclear Translocation to Prevent Oxidative Damage
    Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage Xuanye Caoa,1, Chaoqun Lia,1, Siyu Xiaoa,1, Yunlan Tanga, Jing Huanga, Shuan Zhaoa, Xueyu Lia, Jixi Lia, Ruilin Zhanga, and Wei Yua,2 aState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai 200438, People’s Republic of China Edited by Wei Gu, Columbia University, New York, NY, and accepted by Editorial Board Member Carol Prives December 9, 2016 (received for review May 26, 2016) Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential investigated in recent years (9–12). Acetylation regulates diverse aminoacylation function in protein synthesis. Recently, TyrRS has cellular processes, including gene silencing (13), oxidative stress been shown to translocate to the nucleus and protect against DNA (13, 14), DNA repair (15), cell survival and migration (16, 17), and damage due to oxidative stress. However, the mechanism of TyrRS metabolism (9, 18, 19). Most acetylated proteins act as transcrip- nuclear localization has not yet been determined. Herein, we report tion factors in the nucleus and as metabolic enzymes outside the that TyrRS becomes highly acetylated in response to oxidative nucleus (9). Strikingly, the acetylation of multiple aminoacyl- stress, which promotes nuclear translocation. Moreover, p300/ tRNA synthetases, including tyrosyl-tRNA synthetase, has been CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 reported in a number of proteomic studies (10, 12). However, the + (SIRT1), a NAD -dependent deacetylase, regulate the nuclear local- link between acetylation and AARS remains to be established. ization of TyrRS in an acetylation-dependent manner.
    [Show full text]