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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

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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.

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Data availability

All data displayed in this publication are available from the corresponding author upon request.

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Acknowledgements

The authors extend their appreciation to the Researchers Supporting Project Number (RSPD2024R723), King Saud University, Riyadh, Saudi Arabia.

Funding

This work was supported by King Saud University (Grant No. RSPD2024R723)

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Conceptualization—VV, and GL; methodology—VV, PK; data curation—VV, GK, writing—original draft—GL; software—SP, GK, and PK; formal analysis—PK, and SP; writing—review and editing—SP, PK, GK, funding acquisition—MSA; project administration—MSA. All the authors read the final version of the manuscript and agreed to publish it.

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Correspondence to Growther Lali or Mohamad S. AlSalhi.

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Vahitha, V., Lali, G., Prasad, S. et al. 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 51, 61 (2024). https://doi.org/10.1007/s11033-023-09032-w

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