Synergistic Impact of Copper Oxide Nanoparticles and Intracellular Extract of Lactobacillus paracasei on Viability and Proliferation of K۵۶۲ Leukemia Cells

Background: Copper oxide nanoparticles (CuO NPs) and probiotic intracellular extracts both have different cytotoxic action against cancerous cells. This research was conducted to examine the effective effects of the combination of CuO NPs and probiotic intracellular extracts on the viability and proliferation of K۵۶۲ leukemia cells. Methods: The K۵۶۲ cells were treated with CuO NPs (۰,۱۰,۲۰,۴۰,۸۰,۱۰۰,۲۰۰ng/mL), Lactobacillus paracasei intracellular extract (۰,۵۰,۱۰۰,۲۰۰,۴۰۰,۸۰۰,۱۶۰۰µg/mL), and their combination at respective IC۵۰ concentration for ۲۴, ۴۸, and ۷۲ hours. Cell viability was assessed by MTT assay, reflecting mitochondrial metabolic activity, and Neutral Red uptake assay, expressing lysosomal integrity and membrane function. Results: Both the anticancer activity of copper oxide nanoparticles (CuO NPs) and intracellular Lactobacillus paracasei extract had a clear time-dependent effect. ۷۲ hours following treatment, the IC۵۰ measured by the MTT assay were ۴۰۰ ng/mL for CuO NPs and ۷۰۰ µg/mL for L. paracasei extract, signifying mitochondrial metabolic inhibition. In contrast, the Neutral Red uptake assay for lysosomal and membrane integrity provided IC۵۰ values of ۱۰۰ ng/mL for CuO NPs and ۲۲۱۰ µg/mL for L. paracasei extract. More importantly, co-treatment at these IC۵۰ doses for ۷۲ hours yielded a ۳۷% loss in mitochondrial activity and a ۵۰% loss in lysosomal activity, far greater than in the cytotoxic effect of individual agents. We examined the details of this interaction using the median-effect method. The combination index (CI) values were below ۱ for treatments involving combined CuO NPs and intracellular Lactobacillus paracasei extract suggesting a synergistic effect on K۵۶۲ cell growth. Conclusion: Such synergistic effects, by combining antimetabolite effects and through inhibition of mitochondrial functions, indicate a potential adjuvant treatment approach for leukemia.

کلیدواژه ها:

Copper Oxide Nanoparticles ، Intracellular extract ، Lactobacillus paracasei ، K۵۶۲ cancer cell line ، Synergistic effect