Unveiling the therapeutic potential of thymol from Nigella sativa L. seed: selective anticancer action against human breast cancer cells (MCF-7) through down-regulation of Cyclin D1 and proliferative cell nuclear antigen (PCNA) expressions

Mol Biol Rep. 2024 Jan 3;51(1):61. doi: 10.1007/s11033-023-09032-w.

Abstract

Background: Breast adenocarcinoma cells (MCF-7) are characterized by the overexpression of apoptotic marker genes and proliferative cell nuclear antigen (PCNA), which promote cancer cell proliferation. Thymol, derived from Nigella sativa (NS), has been investigated for its potential anti-proliferative and anticancer properties, especially its ability to suppress Cyclin D1 and PCNA expression, which are crucial in the proliferation of cancer cells.

Methods: The cytotoxicity of thymol on MCF-7 cells was assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release methods. Thymol was tested at increasing concentrations (0-1000 µM) to evaluate its impact on MCF-7 cell growth. Additionally, Cyclin D1 and PCNA gene expression in thymol-treated and vehicle control groups of MCF-7 were quantified using real-time Polymerase Chain Reaction (RT-qPCR). Protein-ligand interactions were also investigated using the CB-Dock2 server.

Results: Thymol significantly inhibited MCF-7 cell growth, with a 50% inhibition observed at 200 µM. The gene expression of Cyclin D1 and PCNA was down-regulated in the thymol-treated group relative to the vehicle control. The experimental results were verified through protein-ligand interaction investigations.

Conclusions: Thymol, extracted from NS, demonstrated specific cytotoxic effects on MCF-7 cells by suppressing the expression of Cyclin D1 and PCNA, suggesting its potential as an effective drug for MCF-7. However, additional in vivo research is required to ascertain its efficacy and safety in medical applications.

Keywords: Cyclin D1; Gene expression; MCF-7; MTT; Nigella sativa; Thymol.

MeSH terms

  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism
  • Antigens, Nuclear / therapeutic use
  • Breast Neoplasms* / genetics
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Down-Regulation
  • Female
  • Humans
  • Ligands
  • MCF-7 Cells
  • Nigella sativa* / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Thymol / pharmacology
  • Thymol / therapeutic use

Substances

  • Proliferating Cell Nuclear Antigen
  • Thymol
  • Antigens, Nuclear
  • Cyclin D1
  • Ligands