Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization
Journal
Toxicology and Applied Pharmacology
Journal Volume
218
Journal Issue
2
Pages
143-151
Date Issued
2007
Author(s)
Chang M.-C.
Chan C.-P.
Wang Y.-J.
Lee P.-H.
Chen L.-I.
Abstract
Sanguinarine is a benzopheanthridine alkaloid present in the root of Sanguinaria canadensis L. and Chellidonium majus L. In this study, sanguinarine (2 and 3?μM) exhibited cytotoxicity to KB cancer cells by decreasing MTT reduction to 83% and 52% of control after 24-h of exposure. Sanguinarine also inhibited the colony forming capacity (> 52-58%) and growth of KB cancer cells at concentrations higher than 0.5-1?μM. Short-term exposure to sanguinarine (> 0.5?μM) effectively suppressed the adhesion of KB cells to collagen and fibronectin (FN). Sanguinarine (2 and 3?μM) induced evident apoptosis as indicated by an increase in sub-G0/G1 populations, which was detected after 6-h of exposure. Only a slight increase in cells arresting in S-phase and G2/M was noted. Induction of KB cell apoptosis and necrosis by sanguinarine (2 and 3?μM) was further confirmed by Annexin V-PI dual staining flow cytometry and the presence of DNA fragmentation. The cytotoxicity by sanguinarine was accompanied by an increase in production of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential as indicated by single cell flow cytometric analysis of DCF and rhodamine fluorescence. NAC (1 and 3?mM) and catalase (2000?U/ml) prevented the sanguinarine-induced ROS production and cytotoxicity, whereas dimethylthiourea (DMT) showed no marked preventive effect. These results suggest that sanguinarine has anticarcinogenic properties with induction of ROS production and mitochondrial membrane depolarization, which mediate cancer cell death. ? 2006 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
acetylcysteine; catalase; collagen; dimethylthiourea; DNA fragment; fibronectin; lipocortin 5; propidium iodide; reactive oxygen metabolite; rhodamine; sanguinarine; antineoplastic activity; apoptosis; article; cancer; cancer cell culture; cancer cell destruction; cell adhesion; cell cycle G0 phase; cell cycle G1 phase; cell cycle G2 phase; cell cycle M phase; cell cycle S phase; cell death; Chellidonium majus; controlled study; drug cytotoxicity; drug effect; flow cytometry; fluorescence; human; human cell; medicinal plant; membrane depolarization; mitochondrial membrane; Sanguinaria; sanguinaria canadensis; Acetylcysteine; Alkaloids; Annexin A5; Anticarcinogenic Agents; Antioxidants; Apoptosis; Benzophenanthridines; Catalase; Cell Adhesion; Cell Cycle; Cell Proliferation; Collagen; DNA Fragmentation; Fibronectins; Flow Cytometry; Humans; Isoquinolines; KB Cells; Membrane Potentials; Mitochondrial Membranes; Necrosis; Reactive Oxygen Species; Thiourea; Tumor Stem Cell Assay; Sanguinaria canadensis
Type
journal article