Tanshinone IIA isolated from Salvia miltiorrhiza elicits the cell death of human endothelial cells
Journal
Journal of Biomedical Science
Journal Volume
12
Journal Issue
2
Pages
347-361
Date Issued
2005
Author(s)
Abstract
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. ? 2005 National Science Council.
SDGs
Other Subjects
antineoplastic agent; cytochrome c; herbaceous agent; reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone); reduced nicotinamide adenine dinucleotide phosphate; Salvia miltiorrhiza extract; tanshione iia; unclassified drug; article; calcium cell level; carcinoma cell; controlled study; cytotoxicity; drug effect; drug potency; endothelium cell; enzyme activation; enzyme activity; human; human cell; membrane potential; mitochondrial membrane; neovascularization (pathology); oxidative stress; priority journal; Acridine Orange; Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Calcium; Caspases; Cell Cycle; Cell Death; Cytochromes c; Dicumarol; Drugs, Chinese Herbal; Egtazic Acid; Electrophoresis, Polyacrylamide Gel; Endothelial Cells; Enzyme Activation; Enzyme Inhibitors; Humans; Membrane Potentials; Mitochondria; Models, Biological; NAD(P)H Dehydrogenase (Quinone); Oxidative Stress; Phenanthrenes; Plant Extracts; Reactive Oxygen Species; Salvia miltiorrhiza; Time Factors; Salvia miltiorrhiza
Type
journal article