Cytotoxicity of p-tyrosol and its derivatives may correlate with the inhibition of DNA replication initiation
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- Published online on: February 1, 2008 https://doi.org/10.3892/or.19.2.527
- Pages: 527-534
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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 α-primase), especially pol α-primase. These results suggest that p-tyrosyl gallate-induced cell cycle arrest during S phase correlates with the inhibition of DNA replication. Pol α-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.