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

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.

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

“…In cancer cells, PC3 are well known as lipid-dependent cells, and mainly utilize FAs from the external environment as energy for cell growth. 23 Therefore, the overexpression of free fatty receptors (FFARs) or CD36 membrane protein for the uptake of long-chain FAs extensively pronounced in previous studies for the PC3 cell line could be advantageous for the higher uptake of LSC as compared to LLC. 41 On the other hand, the lower expression of FA receptors could reduce the active transport of LFCs through the cell membrane of normal cells; thereby the cytotoxicity against normal cell lines could be explained through the self-assembled behaviors of LFCs.…”

“…Finally, we examined the direct antiproliferative effect of three LFCs on the PC3 cell line. PC3 is a hormone-insensitive prostate cancer cell line and PCa is reported as a lipid-dependent tumor; 23 therefore it would be clearer to understand the impacts of conjugated fatty acids on the direct inhibitory effects of LFNs as compared to that of LEU. Together with 2D cell cultures, a three-dimensional (3D) spheroid culture assay was performed in this study mimicking solid tumors to observe and understand the anticancer activity of LFNs.…”

Evaluation of the Antibacterial Activity of Isatin against Campylobacter jejuni and Campylobacter coli Strains

“…The cytotoxicity value of isatin (IC 50 = 125.63 µg/mL for MRC-5 cell line derived from normal human lung tissue) was higher than that of ciprofloxacin; that is, with IC 50 = 23.89 µg/mL (72.1 mM for RWPE-1 cell line from normal human epithelial prostate cells) [45], this indicates that isatin is less toxic despite the different cell lines assayed.…”

Erucic Acid—Both Sides of the Story: A Concise Review on Its Beneficial and Toxic Properties

“…The results showed an almost two-fold increase in the cytotoxic activity of the combination of ciprofloxacin and moxifloxacin with EA when compared to the compounds alone. However, other fatty acids used in the study were more potent [ 31 , 32 ]. A similar effect was observed in further studies by the same group of authors as other prostate cancers (LNCaP and DU-145) and normal (RWPE-1) cell lines.…”

“…A similar effect was observed in further studies by the same group of authors as other prostate cancers (LNCaP and DU-145) and normal (RWPE-1) cell lines. EA conjugate with ciprofloxacin showed increased, but still moderate cytotoxicity, with IC 50 ranging from 27.6 to 73.3 µM, and 60.8 µM for cancer and normal prostate cells, respectively [ 32 ].…”