Gallic acid provokes DNA damage and suppresses DNA repair gene expression in human prostate cancer PC-3 cells.

Abstract

Our earlier studies have demonstrated that gallic acid (GA) induced cytotoxic effects including induction of apoptosis and DNA damage and inhibited the cell migration and invasion in human cancer cells. However, GA-affected DNA damage and repair gene expressions in human prostate cancer cells are still unclear. In this study, we investigated whether or not GA induces DNA damage and inhibits DNA repair gene expression in a human prostate cancer cell line (PC-3). The results from flow cytometric assay indicated that GA decreased the percentage of viable PC-3 cells in a dose- and time-dependent manner. PC-3 cells after exposure to different doses (50, 100, and 200 μM) of GA and various periods of time (12, 24, and 48 h) led to a longer DNA migration smear (comet tail) occurred based on the single cell gel electrophoresis (comet assay). These observations indicated that GA-induced DNA damage in PC-3 cells, which also confirmed by 4,6-diamidino-2-phenylindole dihydrochloride staining and DNA agarose gel electrophoresis. Alternatively, results from real-time polymerase chain reaction assay also indicated that GA inhibited ataxia telangiectasia mutated, ataxia-telangiectasia and Rad3-related, O⁶-methylguanine-DNA methyltransferase, DNA-dependent serine/threonine protein kinase, and p53 mRNA expressions in PC-3 cells. Taken together, the present study showed that GA caused DNA damage and inhibited DNA repair genes as well as both effects may be the critical factors for GA-inhibited growth of PC-3 cells in vitro.

• Authors: Kuo-Ching Liu, Heng-Chien Ho, An-Cheng Huang, Bin-Chuan Ji, Hui-Yi Lin, Fu-Shin Chueh, Jai-Sing Yang, Chi-Cheng Lu, Jo-Hua Chiang, Menghsiao Meng, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 28 Issue 10 Pg. 579-87 (Oct 2013) ISSN: 1522-7278 [Electronic] United States
• PMID: 21887735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc., a Wiley company.

Chemical References

• Cell Cycle Proteins
• DNA-Binding Proteins
• Tumor Suppressor Proteins
• Gallic Acid
• O(6)-Methylguanine-DNA Methyltransferase
• ATM protein, human
• ATR protein, human
• Ataxia Telangiectasia Mutated Proteins
• DNA-Activated Protein Kinase
• Protein Serine-Threonine Kinases

Topics

• Apoptosis (drug effects)
• Ataxia Telangiectasia Mutated Proteins
• Cell Cycle Proteins (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Comet Assay
• DNA Damage (drug effects)
• DNA Repair (drug effects)
• DNA-Activated Protein Kinase (antagonists & inhibitors, genetics, metabolism)
• DNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• Gallic Acid (pharmacology)
• Gene Expression
• Humans
• Male
• O(6)-Methylguanine-DNA Methyltransferase (antagonists & inhibitors, genetics, metabolism)
• Prostatic Neoplasms
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Tumor Suppressor Proteins (antagonists & inhibitors, genetics, metabolism)