The modulatory effects of two bioflavonoids, quercetin and thymoquinone on the expression levels of DNA damage and repair genes in human breast, lung and prostate cancer cell lines.

Abstract

The recent decade has witnessed the increasing potential of various flavonoids such as quercetin and thymoquinone in inhibiting cancer cells proliferation and growth and their therapeutic effects in various cancers. Therefore, in the current study, we aim to evaluate the expression levels of key factors of DNA damage response in human breast, lung and prostate cancer cell lines in response to treatment with quercetin and thymoquinone. MTT assay was applied to assess the effects of quercetin and thymoquinone on the viability of MCF-7, A549, and PC3 cancer cells. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the expression levels of p53, RAD51, Ku70, XRCC1, and H2AX in treated cells. In addition, the expression rate of 8-hydroxy-deoxyguanosine (8-OH-dG) was assessed by ELISA kit. The quercetin and thymoquinone induce cytotoxicity in breast, lung, and prostate cancer cells effectively; MCF-7 cells were the most sensitive cells to quercetin with an IC50 value of 50μM and PC3 cells were more sensitive to thymoquinone with an IC50 value of 20μM. The expression levels of DNA damage markers, H2AX, and 8-OH-dG were significantly increased in all cancer cells treated with quercetin and thymoquinone (p<0.05). Moreover, both flavonoids significantly decreased the expression levels of DNA repair mediators, RAD51, Ku70, XRCC1, in cell lines. P53 was also increased in MCF-7 and A549 cells. We concluded that quercetin and thymoquinone may exert their effects through modulation of DNA damage response, increasing DNA damage, and suppressing DNA repair genes.