Cytotoxicity of p-tyrosol and its derivatives may correlate with the inhibition of DNA replication initiation.

Abstract

p-Tyrosol is a phenolic compound present in different dietary sources that can exert mild antioxidant properties based on in vitro and in vivo studies. In our study, two p-tyrosol derivatives (p-tyrosyl gallate and p-tyrosyl acetate) were synthesized and compared together with p-tyrosol and gallic acid for their cytotoxic activities on human cancer cells. p-Tyrosyl gallate had the most potent cytotoxicity and the major cytotoxic mechanism of its action was studied. We found that in HeLa cells, p-tyrosyl gallate can effectively induce cell cycle arrest during S phase and inhibited in vitro simian virus (SV40 DNA) replication. In addition, p-tyrosyl gallate can inhibit three important functional replication proteins (topoisomerase I, RPA and pol alpha-primase), especially pol alpha-primase. These results suggest that p-tyrosyl gallate-induced cell cycle arrest during S phase correlates with the inhibition of DNA replication. Pol alpha-primase may be the main target molecule. Taken together, we suggest that p-tyrosyl gallate is a strong anticancer drug candidate that warrants further investigation.

• Authors: Eun-Young Ahn, Yahong Jiang, Yanjun Zhang, Eun Mi Son, Song You, Shin-Won Kang, Jang-Su Park, Jee H Jung, Burm-Jong Lee, Dong-Kyoo Kim
• Journal: Oncology reports (Oncol Rep) Vol. 19 Issue 2 Pg. 527-34 (Feb 2008) ISSN: 1021-335X [Print] Greece
• PMID: 18202803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• DNA, Single-Stranded
• Enzyme Inhibitors
• p-tyrosyl acetate
• p-tyrosyl gallate
• 4-hydroxyphenylethanol
• DNA Primase
• DNA polymerase alpha-primase
• DNA Polymerase I
• Phenylethyl Alcohol

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Cycle (drug effects)
• DNA Polymerase I (antagonists & inhibitors)
• DNA Primase (antagonists & inhibitors)
• DNA Replication (drug effects)
• DNA, Single-Stranded (drug effects, metabolism)
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• HeLa Cells
• Humans
• Phenylethyl Alcohol (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Simian virus 40 (drug effects)