Effect of quercetin on the genotoxic potential of cisplatin

Abstract

The natural product flavonoid quercetin has been shown to sensitise cells to the cytotoxic potential of cisplatin. Both cisplatin and quercetin are genotoxicants. As quercetin is curnntly in clinical trial as a cytotoxicMt-sensitising agent, we wanted to elucidate whether it affects the genotoxicity associated with cisplatin. The genotoxic potential of both agents alone and in combination was studied in Solmonello typhlmurium strains TA 98, TA 100 and TA 102 and by assessment of unscheduled DNA synthesis (UDS) in rat hepatocytes. Furthermore, effects of quercetin on levels of cisplatin-DNA adducts were studied in hepatocytes by ELISA Cisplatin was mutagenic in all 3 bacterial strains and quercetin in strain TA 98. The number of revertant Salmonella colonies observed with the combination did not differ significantly from that caused by the drugs on their own. In the UDS assay, cisplatin was genotoxic but quercetin was not. In combination, quercetin decreased the nuclear grain count caused by cisplatin, but quercetin did not alter the level of cisplatin-DNA adduct formation in hepatocytes. Our results suggest that the mutagenic potential of the combination cisplatin-quercetin, as judged by the bacterial short-tern test, does not exceed that associated with the individual components. However, in hepatocytes, quercetin appears to inhibit repair of cisplatin-induced DNA damage. Therefore, in patients who are to be treated with a combination of cisplatin and quercetin, the risk of genotoxicity in normal tissues will have to be taken into consideration.

Quercetin-induced inhibition and synergistic activity with cisplatin – a chemotherapeutic strategy for nasopharyngeal carcinoma cells

“…The interest in quercetin for therapeutics application is spurred by its ability to sensitize cells to the cytotoxic effects of platinum-containing drugs [16]. However, limited research is available on the role of quercetin in NPC and potentiation is seldom defined as additive or synergistic.…”

In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2·4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines

“…Cross et al [42] have shown that cisplatin was mutagenic using the Ames test, suggesting that using cisplatin could lead to an increased risk of secondary malignancies. They conclude that normal cells in patients undergoing treatment with cisplatin were at an increased risk of genotoxicity and that this must be taken into consideration when deciding on cancer treatment with this agent.…”

Biological Flora of the British Isles: Pteridium aquilinum (L.) Kuhn

“…The exact cause of the syndromes 3-5 remains unknown, but a range of chemical constituents of Pteridium (ptaquilosides, quercetin and shikimic acid) has been implicated (Evans 1976a;Smith et al 2000). Chemicals in Pteridium, known to have carcinogenic, cytotoxic, mutagenic, tumorigenic and teratogenic activity, can induce apoptosis and symptoms were radiomimetic (Evans 1976a(Evans , 1986Santos et al 1992;Cross et al 1996;Ngumuo & Jones 1996;Rzymowska et al 1999;Simán et al 2000). Ptaquiloside, for example, has been shown to have a DNA-binding capacity and cleaves DNA (Kigoshi et al 1992).…”

“…Chemicals in Pteridium , known to have carcinogenic, cytotoxic, mutagenic, tumorigenic and teratogenic activity, can induce apoptosis and symptoms were radiomimetic (Evans 1976a, 1986; Santos et al . 1992; Cross et al . 1996; Ngumuo & Jones 1996; Rzymowska et al .…”