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 ptyrosol 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.

A rapid determination of drug candidate tyrosol galactoside in rat plasma by HPLC and its application to the pharmacokinetics study

“…Tyrosol is a naturally occurring phenol with interesting biological properties including anticancer, anti-depressant, stress-protective, cardioprotection, anti-osteoporosis, and antioxidative effects (Ahn et al 2008;Chernyshov et al 2007;Dinnella et al 2007;Panossian et al 2008Panossian et al , 2009Puel et al 2008). In our recent studies, tyrosol was derived for the first time into a novel glycoside named tyrosol galactoside (TG), and the galactoside demonstrated better anti-fatigue effect than tyrosol.…”

Improving process conditions of hydroxytyrosol synthesis by toluene-4-monooxygenase

“…These phenolic compounds naturally present in olives [27][28][29] may also provide added health value. p-Tyrosol, also present in wine and Rhodiola species, has been reported to have various beneficial health properties, including antioxidant and anti-inflammatory activities [28,[30][31][32]. In contrast with the numerous studies on p-tyrosol, there are only few reports regarding m-tyrosol, though it was shown to have bacteriostatic activity similar to that of HTyr and double that of ptyrosol [33].…”

Antimicrobial and Antioxidant Properties of a Bacterial Endophyte, Methylobacterium radiotolerans MAMP 4754, Isolated from Combretum erythrophyllum Seeds

“…Antioxidant activity of phenolic compounds, identified herein, can be described in terms of their intrinsic bioactivity as free radical scavengers or indirectly as modulators of intracellular pro-and antioxidant enzymes [95]. Phenolic compounds have been shown to exert antioxidant properties both in vitro and in vivo [96]. One of the phenolic compounds identified in this study was p-tert-butyl (Table 3).…”