The crude extract of Corni Fructus induces apoptotic cell death through reactive oxygen species-modulated pathways in U-2 OS human osteosarcoma cells.

Abstract

Crude extract of Corni Fructus (CECF) has been used in Traditional Chinese medicine for the treatment of different diseases for hundreds of years. The purpose of this study was to investigate the cytotoxic effects of CECF on U-2 OS human osteosarcoma cells. Flow cytometry was used for measuring the percentage of viable cells, cell-cycle distribution, apoptotic cells in sub-G1 phase, reactive oxygen species (ROS), Ca(2+) levels, and mitochondrial membrane potential (ΔΨm ). Comet assay and 4'-6-diamidino-2-phenylindole staining were used for examining DNA damage and condensation. Western blotting was used to examine apoptosis-associated protein levels in U-2 OS cells after exposed to CECF. Immunostaining and confocal laser system microscope were used to examine protein translocation after CECF incubation. CECF decreased the percentage of viability, induced DNA damage and DNA condensation, G₀/G₁ arrest, and apoptosis in U-2 OS cells. CECF-stimulated activities of caspase-8, caspase-9, and caspase-3, ROS, and Ca(2+) production, decreased ΔΨm levels of in U-2 OS cells. CECF increased protein levels of caspase-3, caspase-9, Bax, cytochrome c, GRP78, AIF, ATF-6α, Fas, TRAIL, p21, p27, and p16 which were associated with cell-cycle arrest and apoptosis. These findings suggest that CECF triggers apoptosis in U-2 OS cells via ROS-modulated caspase-dependent and -independent pathways.

• Authors: Ching-Lung Liao, Shu-Chun Hsu, Chien-Chih Yu, Jai-Sing Yang, Nou-Ying Tang, Wellington Gibson Wood, Jaung-Geng Lin, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 29 Issue 9 Pg. 1020-31 (Sep 2014) ISSN: 1522-7278 [Electronic] United States
• PMID: 23239598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Neoplasm Proteins
• Plant Extracts
• Reactive Oxygen Species
• DNA
• Caspases

Topics

• Apoptosis (drug effects)
• Bone Neoplasms (enzymology, metabolism, pathology)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cornus (chemistry)
• DNA (drug effects)
• Endoplasmic Reticulum Chaperone BiP
• Humans
• Medicine, Chinese Traditional
• Membrane Potential, Mitochondrial (drug effects)
• Neoplasm Proteins (metabolism)
• Osteosarcoma (enzymology, metabolism, pathology)
• Plant Extracts (pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)