In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. 2003

Ahmed M Shoieb, and Mona Elgayyar, and Paul S Dudrick, and John L Bell, and Patricia K Tithof
Department of Pathology, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996-4543, USA.

Thymoquinone (TQ) is likely responsible for the chemotherapeutic effects of N. sativa extract; however, the cellular mechanisms remain ill-defined. TQ-induced cytotoxicity was investigated using canine osteosarcoma (COS31), its cisplatin-resistant variant (COS31/rCDDP), human breast adenocarcinoma (MCF7), human ovarian adenocarcinoma (BG-1) and Madin-Darby canine (MDCK) cell lines. TQ-induced cytotoxicity was determined using a proliferation assay (MTT assay) and apoptosis assays. Effects of TQ on the cell cycle were determined using flow cytometry. COS31/rCDDP resistant cells were the most sensitive cell line to TQ and MDCK cells were the least sensitive. TQ (25 micro M) induced apoptosis of COS31 cells 6 h after treatment and decreased the number of COS31 cells in S-phase and increased cells in G1-phase, indicating cell cycle arrest at G1. These results suggest that TQ kills cancer cells by a process that involves apoptosis and cell cycle arrest. Non-cancerous cells are relatively resistant to TQ.

UI MeSH Term Description Entries
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D005982 Glutathione Transferase A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. Glutathione S-Alkyltransferase,Glutathione S-Aryltransferase,Glutathione S-Epoxidetransferase,Ligandins,S-Hydroxyalkyl Glutathione Lyase,Glutathione Organic Nitrate Ester Reductase,Glutathione S-Transferase,Glutathione S-Transferase 3,Glutathione S-Transferase A,Glutathione S-Transferase B,Glutathione S-Transferase C,Glutathione S-Transferase III,Glutathione S-Transferase P,Glutathione Transferase E,Glutathione Transferase mu,Glutathione Transferases,Heme Transfer Protein,Ligandin,Yb-Glutathione-S-Transferase,Glutathione Lyase, S-Hydroxyalkyl,Glutathione S Alkyltransferase,Glutathione S Aryltransferase,Glutathione S Epoxidetransferase,Glutathione S Transferase,Glutathione S Transferase 3,Glutathione S Transferase A,Glutathione S Transferase B,Glutathione S Transferase C,Glutathione S Transferase III,Glutathione S Transferase P,Lyase, S-Hydroxyalkyl Glutathione,P, Glutathione S-Transferase,Protein, Heme Transfer,S Hydroxyalkyl Glutathione Lyase,S-Alkyltransferase, Glutathione,S-Aryltransferase, Glutathione,S-Epoxidetransferase, Glutathione,S-Transferase 3, Glutathione,S-Transferase A, Glutathione,S-Transferase B, Glutathione,S-Transferase C, Glutathione,S-Transferase III, Glutathione,S-Transferase P, Glutathione,S-Transferase, Glutathione,Transfer Protein, Heme,Transferase E, Glutathione,Transferase mu, Glutathione,Transferase, Glutathione,Transferases, Glutathione
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D016193 G1 Phase The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors. First Gap Phase,G1a Phase,G1b Phase,Gap Phase 1,First Gap Phases,G1 Phases,G1a Phases,G1b Phases,Gap Phase, First,Gap Phases, First,Phase 1, Gap,Phase, First Gap,Phase, G1,Phase, G1a,Phase, G1b,Phases, First Gap,Phases, G1,Phases, G1a,Phases, G1b
D016227 Benzoquinones Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. 1,2-Benzoquinones,1,4-Benzoquinones,Benzodiones,2,5-Cyclohexadiene-1,4-Diones,o-Benzoquinones,p-Benzoquinones

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