The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines—Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

SIMPLE SUMMARY: Most prostate cancers are initially hormone-dependent but later gain a hormone-independent phenotype associated with changes in lipid metabolism, including enhanced absorption of extracellular fatty acids. The aim of our study was to assess the effect of ciprofloxacin conjugates with fatty acids on different type of prostate cancer (LNCaP and DU-145) and normal (RWPE-1) cells, as well as their influence on cell lipid metabolism by proteomic analysis. All tested conjugates exhibited cytotoxic potential, the most powerful for oleic, elaidic and docosahexaenoic acids. The hormone-independent DU145 line was more sensitive to derivatives than the hormone-dependent LNCaP line. These results are consistent with previously observed pronounced cytotoxic effect of conjugates on a hormone-insensitive PC3 line. Tested derivatives decreased intensity of proteins involved in prostate cancer lipid metabolism. Our findings confirm the involvement of lipid metabolism in prostate carcinogenesis indicating a target for fatty acids as drug carriers. ABSTRACT: Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress.