Effects of 5-Fluorouracil, Thymoquinone, and Mammary Stem Cells' Exosomes on in Vitro Cultured Breast Cancer Cells.

Background: 5-fluorouracil (5 -FU) is an antimetabolic agent used for treating slowly growing solid tumors like breast and ovarian carcinoma. Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa , it has been found to demonstrate anticancerous effects in several preclinical studies, and this is because TQ possesses multitarget nature. Stem cells -derived exosomes are in the spotlight of research and are promising tissue regenerative and anticancer cell -derived nanovesicles. Aim: Herein, we studied the antineoplastic effects of Exosomes derived from mammary stem cells (MaSCs-Exo) on breast cancer cells, alone or combined with TQ when compared to a breast cancer chemotherapeutic agent; 5 -FU. Methods: Our approach included performing viability test and measuring the expression of pro-apoptotic gene (Bax), anti-apoptotic gene (BCL-2) and angiogenic gene (VEGF) on Human MCF-7 cells (breast adenocarcinoma cells), the MCF-7 cells were cultured and incubated with medium containing 5 -FU (25 mu g/ml), TQ (200 mu g/ml), MaSCs-Exo (100 mu g protein equivalent), a combination of TQ (200 mu g/ml) and MaSCs-Exo (100 mu g). Results: Our obtained results show that TQ and MaSCs-Exo each can effectively inhibit breast cancer cell line (MCF7) proliferation and growth. Also, the results show that the combination of TQ and MaSCs-Exo had higher cytotoxic effects on MCF-7 breast cancer cells than TQ or 5 -FU, alone. Conclusion: The present study shows a promising anticancer potential of exosomes isolated from mammary stem cells; this effect was potentiated by adding TQ with MaSCs-derived exosomes.