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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Caspase Activation, Upregulation of Bax and P53, Downregulation of Bcl-2 and Enhanced Generation of Reactive Oxygen Species Mediate the Anti-proliferative and Anti-migratory Activity of Mefenamic Acid in Breast Cancer Cells

Mohammed Mousa AlZharani1, Eman Abdullah Almuqri1, Mohammed Mubarak Ahmed1★, Shaikha A Albatli1, Nada Hamad Aljarba2, Hassan Ahmed Rudayni1, Khadijah Nasser Yaseen3, Saad Hussin Alkahtani3, Fahd Ali Nasr1, Amin Abdullah AlDoaiss4, Mohammed Saad AlEissa1★ Corresponding author

  1. 1Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAUDI ARABIA.
  2. 2Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, SAUDI ARABIA.
  3. 3Department of Zoology, College of Science, King Saud University, Riyadh, SAUDI ARABIA.
  4. 4Department of Biology, College of Science, King Khalid University, Abha, SAUDI ARABIA.

CORRESPONDENCE

Mohammed Mubarak Ahmed

Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAUDI ARABIA.

mohammedahmed62@yahoo.com

Received: 08-11-2024; Revised: 28-01-2025; Accepted: 12-04-2025.

Volume 59, Issue 3 · pp. 1109–1117 · PUBLISHED 2025 · DOI: 10.5530/ijper.20250489

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ABSTRACT

Background: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are among the most prescribed pharmaceuticals worldwide. Similar to other NSAIDs, mefenamic acid possesses anti- inflammatory, analgesic and antipyretic properties. The present study was carried out to further elucidate the antiproliferative activity of mefenamic acid at the molecular level in the human breast cancer cell line (MCF-7). Materials and Methods: The cytotoxic effect of mefenamic acid on breast cancer cells (MCF-7) was assessed using MTT cytotoxicity and Lactate Dehydrogenase (LDH) leakage assays. qRT-PCR analysis was employed to evaluate the expression of the apoptosis-related genes encoding p53, caspases-3, -8 and-9, Bax and Bcl-2. The anti-migratory effect of mefenamic acid on breast cancer cells was evaluated by using the scratch assay. H2DCFDA (H2-DCF, DCF) cellular assay was employed to estimate the intracellular generation of Reactive Oxygen Species (ROS) in breast cancer cells. Results: A significant decrease in the viability (survival rate) of MCF-7 cells was revealed by MTT cytotoxicity and LDH release assays. Compared to the untreated control cells, there were over-expression of p53, caspases-3, -8 and-9 activities. Bax was significantly upregulated and conversely, Bcl-2 showed significant downregulation. Mefenamic acid significantly inhibited the migration of MCF-7 cells as evidenced by the relatively increased distance between the opposing scratch edges. Comparatively, mefenamic acid enhanced the intracellular generation of ROS in breast cancer cells. Conclusion: Based on the present findings, it was concluded that mefenamic acid can exert anti-proliferative and anti-migratory activity in the human breast cancer cell line. Mefenamic acid could be considered a promising anti-cancer agent in combination with other therapies in the treatment of breast cancer.

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    AlZharani, M. M., Almuqri, E. A., Ahmed, M. M., Albatli, S. A., Aljarba, N. H., Rudayni, H. A., Yaseen, K. N., Alkahtani, S. H., Nasr, F. A., AlDoaiss, A. A., & AlEissa, M. S. (2025). Caspase Activation, Upregulation of Bax and P53, Downregulation of Bcl-2 and Enhanced Generation of Reactive Oxygen Species Mediate the Anti-proliferative and Anti-migratory Activity of Mefenamic Acid in Breast Cancer Cells. Indian Journal of Pharmaceutical Education and Research, 59(3), 1109–1117. https://doi.org/10.5530/ijper.20250489