Abstract 3876: Thymoquinone induces the expression of clock genes in breast cancer cells

Abstract

Abstract Thymoquinone is naturally occurring bioactive compound which showed cumulative preclinical evidence of anticancer effects. However, its exact anti-cancer activity remains to be elusive and is currently being studied. In this study, we assessed the role of thymoquinone as a potential therapy in human breast cancer cell lines in addition to its role in altering molecular clock genes expression, which in turn has been associated with tumorgenesis. Sulfa-Rhodamine-B assay (SRB) assay was used to evaluate the cytotoxic effect of thymoquinone in breast cancer cell lines (MCF-7 and T47D). Following 72 h of exposure, thymoquinone showed cytotoxic effects against MCF-7 and T47D with IC50’s of 44.4±3 µM and 152±11 µM respectively. Further investigation showed that thymoquinone showed some affect on the cell cycle distribution in both cell lines. It significantly increased the cell population in S-phase in MCF-7cells (P<0.05), while causing a significant G1 phase arrest in T47D cells (p<0.01). Interestingly, treatment of both cell lines with non-cytotoxic concentrations of thymoquinone resulted in a significant increased expression of clock genes, measured by reverse transcription–quantitative PCR (RT-qPCR). Thymoquinone appeared to increase the expression of BMAL-1 (1.4±0.1 fold), CLOCK (3.4±0.9 fold), PER-1(5.6±0.5 fold), CRY-1 (4.4±0.4 fold), CRY-2(2.2±0.6 fold) in MCF-7 cells. Similarly, thymoquinone increased the expression of BMAL-1 (1.4±0.3 fold), CLOCK (1.4±0.3 fold), PER-1(1.4±0.3 fold), CRY-1 (1.5±0.4 fold), and CRY-2 (1.8±0.1 fold) in T47D cells . In conclusion, thymoquinone possesses a potential in combating breast cancer alone. Despite the promising anti-proliferative activity of thymoquinone against breast cancer cells, the better understanding of these effects is needed to provide a novel approach for the treatment of breast cancer as a disease. Here, we postulate that the drug could be modulating clock genes expression, which ultimately can affect key molecules in cell cycle and cell proliferation. Further studies are needed to confirm this and to elucidate the exact underlying mechanism. Citation Format: Aliaa A. Alamoudi, Hanan A. Bashmail, Ghada M. Ajabnoor, Hani Choudhry, Mohammed A. Hassan, Alia M. Aldahlawi, Ahmed A. Al-abd. Thymoquinone induces the expression of clock genes in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3876.