Thymoquinone decreases cell proliferation and immune evasion of breast cancer cells by reducing CD55 and CD114 levels.

Controlling the proliferation and immune evasion of cancer cells can lead to effective strategies for cancer treatment. Thymoquinone, a bioactive compound derived from Nigella sativa exhibits a potent anti-tumor activity. It can be used as a therapeutic approach because it stabilizes the G-quadruplex structure in the promoter regions of oncogenes. This study aims to investigate the effects of thymoquinone on CD55, an inhibitor of the complement system, and CD114, which is involved in cancer cell proliferation. Real-time PCR and Western blot were conducted to verify the expression of CD55 and CD114 in patients' tumor samples, HMEC cells, MCF-7 cells, and MCF7-cancer stem cells (MCF7-CSCs). MCF-7 cells were treated with thymoquinone, and their biological behavior was evaluated using proliferation, migration, and wound-healing assays. The result indicated that CD55 and CD114 were induced among the patient's samples. The same result is followed by MCF-7 cells and MCF7-CSCs. Treatment of MCF-7 and MCF7-CSCs with thymoquinone effectively downregulated CD55 and CD114 and suppressed the stemness markers Sox2 and Nanog. Promoter analysis revealed the putative G-quadruplex sequences in the CD55 and CD114 genes. Thymoquinone binds to them at the CD55 and CD114 promoters, thereby limiting mRNA expression. Additionally, the inhibition of their expression reduced cell movement and growth, as verified by biological assays. In summary, treating breast cancer cells with thymoquinone could stabilize the G-quadruplex structure on the promoter regions of CD55 and CD114 and hinder their mRNA expression. Therefore, restoring immune recognition and inhibition of proliferation. Hence, thymoquinone could be a potent target for breast cancer therapeutics.