Cytotoxic, cytostatic and anti-estrogenic effect of Thymoquinone on estrogen receptor-positive breast cancer MCF7 cell line

About 80% of breast cancers are estrogen-receptor positive. The research carried out herein focused on the effect of Thymoquinone which is an active compound of Nigella sativa seed on estrogen-receptor positive breast cancer MCF7 cell line. The percentage of apoptotic cells was found using Annexin V-FITC apoptosis detection kit. CycleTEST PLUS DNA Reagent was used to distinguish distribution of treated cells between different cell cycle phases. DNA microarray identified the regulated genes, level of expressed genes, gene ontology and pathway networks. Significant arrest of treated cells at G1 phase suggested cytostatic effect of Thymoquinone 100 μM after 24 hours at p-value < 0.05 which was similar to anti-estrogenic compounds such as Tamoxifen. Cytotoxic effect of Thymoquinone 100 μM was found through highly significant accumulation of cells at sub-G1 phase after 72 hours at p-value < 0.0001. CYP1A1, CYP1B1, NQO1 and UGT1A8 genes were down regulated after 24 hours treatment with Thymoquinone 50 μM concentration which suggested reduction of catechol estrogens and rising in metoxy forms of estradiol and estrone. Reduction of ER would be predictable due to the down-regulation of CYP1B1 and UGT1A8 genes which reduced affinity of trans-tamoxifen-o-glucuronide to ER. The study proposed the benefits of using Thymoquinone to accelerate Tamoxifen effects in treating breast cancer and reducing its side effects.