Effects of 5-fluorouracil, thymoquinone, and mammary stem cells' exosomes on in vitro cultured breast cancer cells

Open Vet J. 2024 Jan;14(1):525-533. doi: 10.5455/OVJ.2024.v14.i1.47. Epub 2024 Jan 31.


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 μg/ml), TQ (200 μg/ml), MaSCs-Exo (100 μg protein equivalent), a combination of TQ (200 μg/ml) and MaSCs-Exo (100 μg).

Results: Our obtained results show that TQ and MaSCs-Exo each can effectively inhibit breast cancer cell line (MCF-7) 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.

Keywords: 5-fluorouracil; Anti-tumor; Apoptosis; Breast cancer; Mammary stem cells.

MeSH terms

  • Animals
  • Antineoplastic Agents*
  • Apoptosis
  • Benzoquinones*
  • Breast Neoplasms* / veterinary
  • Cell Line, Tumor
  • Exosomes* / metabolism
  • Exosomes* / pathology
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Stem Cells / metabolism
  • Stem Cells / pathology


  • Fluorouracil
  • thymoquinone
  • Antineoplastic Agents
  • Benzoquinones