Non-steroidal anti-inflammatory drugs (NSAIDs) regimens enhance synergistic selective anticancer efficacy of chemotherapeutic agents on cultured cells.

BACKGROUND/PURPOSE: Cancer incidences are rising, presenting challenges due to severe side effects and resistance of chemotherapeutic agents. To address these issues, we propose a strategy involving pharmaceutical compositions of PTM (Phytopolyphenols, Targeting drugs, Metals) regimens. This study aimed to investigate NSAIDs (Non-steroidal anti-inflammatory drugs)-PTM regimens enhancing anticancer selectivity and efficacy of chemotherapeutic agents on cultured cancer cells. MATERIALS AND METHODS: Effects of drugs on proliferation of cultured cancer cells and pathogens was assessed using MTT assay and optical density at 600 nm (OD600) respectively. Synergistic effects of drug combinations were determined using combination index and efficacy index. ATPase activity was assayed using a colorimetric method. RESULTS: NSAIDs-PTM regimens demonstrated selective and synergistic anticancer effects. They also enhanced anticancer selectivity and efficacy of Cisplatin, 5-Fluorouracil, and Methotrexate. The most effective NSAIDs-PTM regimens increased anticancer efficacy by 16, 4, and 23 fold against oral, lung, and colon cancer cell lines, respectively. Additionally, these NSAIDs-PTM regimens enhanced selective anticancer efficacy of Cisplatin, 5-Fluorouracil, and Methotrexate by 8-21 fold on the three cancer cells. Furthermore, all regimens exhibited synergistic anti-efflux pump ATPase activity and antibacterial effects against four cultured pathogens. CONCLUSION: The findings indicate that NSAIDs-PTM regimens not only possess synergistic and selective anticancer and antibacterial properties but also enhance anticancer selectivity and efficacy of Cisplatin, 5-Fluorouracil, and Methotrexate. Notably, all regimens exhibited anti-efflux pump ATPase, which may help overcome multidrug resistance in cancer treatment. Given that all components of PTM regimens are clinically effective and safe, further clinical studies are warranted.