Tanshinone IIA isolated from Salvia miltiorrhiza elicits the cell death of human endothelial cells. 2005

Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, 155 Li-Nung Street, Sec. 2, Shih-pai,Taipei, 112, Taiwan.

Tanshinone IIA, a major component extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, is known to exhibit potent cytotoxicity against various human carcinoma cells in vitro. However, the mechanism by which tanshinone IIA produces this anti-tumor effect remains unknown. Since anti-neovascularization has generally been regarded as an effective strategy for anti-cancer therapy, we decided to investigate the mechanism underlying tanshinone IIA-mediated death of human endothelial cells. In this study, we demonstrate that tanshinone IIA elicits human endothelial cell death independent of oxidative stress. These events are partially calcium-dependent and actually dependent upon NAD(P)H: quinone oxidoreductase (NQO1) activity. Tanshinone IIA induces an increase in intracellular calcium, which triggers the release of cytochrome c, thus causing loss of the mitochondrial membrane potential (MMP), resulting in the subsequent activation of caspases. Blocking the induction of Ca2+ perturbation with BAPTA-AM partially rescued cells from tanshinone IIA-induced cytotoxicity. Additionally, blocking NQO1 activity with dicoumoral or inhibiting caspase activities with the general caspase inhibitor, z-VAD-fmk, prevented cell death induced by tanshinone IIA. Therefore, our results imply that tanshinone IIA-mediated cytotoxicity against human endothelial cells may occur through activation of NQO1, which induces a calcium imbalance and mitochondrial dysfunction, thus stimulating caspase activity.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010616 Phenanthrenes POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.
D010936 Plant Extracts Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard. Herbal Medicines,Plant Extract,Extract, Plant,Extracts, Plant,Medicines, Herbal
D001728 Dicumarol An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases. Bishydroxycoumarin,Dicoumarin,Dicoumarol
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D004365 Drugs, Chinese Herbal Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China. Chinese Herbal Drugs,Plant Extracts, Chinese,Chinese Drugs, Plant,Chinese Plant Extracts,Extracts, Chinese Plant,Herbal Drugs, Chinese
D004533 Egtazic Acid A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID. EGTA,Ethylene Glycol Tetraacetic Acid,EGATA,Egtazic Acid Disodium Salt,Egtazic Acid Potassium Salt,Egtazic Acid Sodium Salt,Ethylene Glycol Bis(2-aminoethyl ether)tetraacetic Acid,Ethylenebis(oxyethylenenitrile)tetraacetic Acid,GEDTA,Glycoletherdiamine-N,N,N',N'-tetraacetic Acid,Magnesium-EGTA,Tetrasodium EGTA,Acid, Egtazic,EGTA, Tetrasodium,Magnesium EGTA

Related Publications

Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
January 2011, Evidence-based complementary and alternative medicine : eCAM,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
December 1999, Journal of ethnopharmacology,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
September 2008, Life sciences,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
July 2012, Molecules (Basel, Switzerland),
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
May 2004, Biochemical pharmacology,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
January 2013, The American journal of Chinese medicine,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
August 2012, Archives of pharmacal research,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
November 2023, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
November 2018, Journal of natural products,
Li-Jyun Yang, and Chung-Jiuan Jeng, and Hsiu-Ni Kung, and Cheng-Chi Chang, and An-Guor Wang, and Gar-Yang Chau, and Ming-Jaw Don, and Yat-Pang Chau
May 2010, European journal of histochemistry : EJH,
Copied contents to your clipboard!