Naproxen inhibits proliferation and migration of breast cancer cells (MCF-7) through BCL-2 downregulation, CASPASE activation, BAX upregulation, and generation of excess reactive oxygen species (ROS)

INTRODUCTIONNaproxen, chemically known as (S)-6-methoxy-?methyl-1,2-naphthaleneaceticacid, is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) [1,2,3].It has analgesic, anti-inflammatory, and antipyretic properties, effectively relieving pain and treating various inflammatory conditions.Common uses for naproxen include managing arthritis, tendinitis, spondylitis, bursitis, and gout [4,5,6].ABSTRACT: This study explored the antiproliferative activity of naproxen at the molecular level in human breast cancer cell lines, specifically MCF-7.Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide.Like other NSAIDs, naproxen has anti-inflammatory, analgesic, and antipyretic properties.The cytotoxic effects of naproxen on MCF-7 breast cancer cells were assessed using MTT cytotoxicity and lactate dehydrogenase (LDH) leakage assays.Additionally, quantitative reverse transcription PCR (qRT-PCR) was employed to evaluate the expression of apoptosis-related genes, including p53, caspases-3, 8, and 9, Bax, and Bcl 2. The anti-migratory effects of naproxen on breast cancer cells were investigated using a scratch assay.The H2DCFDA (H2-DCF, DCF) cellular assay was used to estimate the intracellular generation of reactive oxygen species (ROS) in breast cancer cells.Results indicated a significant decrease in the viability of MCF-7 cells, as highlighted by both the MTT cytotoxicity and LDH release assays.Compared to the untreated control cells, there was an overexpression of p53 and increased activities of caspases 3, 8, and 9. Bax was significantly upregulated, while Bcl-2 showed significant downregulation.Naproxen also significantly inhibited the migration of MCF-7 cells, as evidenced by the increased distance between the opposing edges of the scratch.In comparison, naproxen enhanced the intracellular generation of ROS in breast cancer cells.Based on these findings, it can be concluded that naproxen exhibits both antiproliferative and anti-migratory activities in the human breast cancer cell line MCF-7.Therefore, naproxen may be considered a promising candidate as an anti-cancer agent, especially when used in combination with other breast cancer therapies.