Immunobiological efficacy and immunotoxicity of novel synthetically prepared fluoroquinolone ethyl 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate

Soňa Jantová; Ema Paulovičová; Lucia Paulovičová; Michaela Janošková; Miroslav Pánik; Viktor Milata

doi:10.1016/j.imbio.2017.10.008

Immunobiological efficacy and immunotoxicity of novel synthetically prepared fluoroquinolone ethyl 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate

Immunobiology. 2018 Jan;223(1):81-93. doi: 10.1016/j.imbio.2017.10.008. Epub 2017 Oct 6.

Authors

Soňa Jantová¹, Ema Paulovičová², Lucia Paulovičová³, Michaela Janošková¹, Miroslav Pánik⁴, Viktor Milata⁵

Affiliations

¹ Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovak Republic.
² Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Bratislava, Slovak Republic. Electronic address: ema.paulovicova@savba.sk.
³ Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Bratislava, Slovak Republic.
⁴ Institute of Management, Slovak University of Technology, Bratislava, Slovak Republic.
⁵ Institute of Organic Chemistry, Catalysis and Petrochemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovak Republic.

PMID: 29030009
DOI: 10.1016/j.imbio.2017.10.008

Abstract

The present study examined the cytotoxicity, anti-cancer reactivity, and immunomodulatory properties of new synthetically prepared fluoroquinolone derivative 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (6FN) in vitro. The cytotoxicity/toxicity studies (concentrations in the range 1-100μM) are focused on the cervical cancer cells HeLa, murine melanoma cancer cells B16, non-cancer fibroblast NIH-3T3 cells and reconstructed human epidermis tissues EpiDerm™. The significant growth inhibition of cancer cells HeLa and B16 was detected. The cytotoxicity was mediated via apoptosis-associated with activation of caspase-9 and -3. After 72h of treatment, the two highest 6FN concentrations (100 and 50μM) induced toxic effect on epidermis tissue EpiDerm™, even the structural changes in tissue were observed with concentration of 100μM. The effective induction of RAW 264.7 macrophages cell-release of pro- and anti-inflammatory T_H1, T_H2 and T_H17 cytokines, with anti-cancer and/or anti-infection activities, respectively, has been revealed even following low-dose exposition.

Keywords: Anticancer; Cytokines; Cytotoxicity; EpiDerm toxicity; Quinolones.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Caspase 9 / metabolism
Cell Growth Processes / drug effects
Cell Survival
Cytokines / metabolism
Epidermis / drug effects*
Epidermis / pathology
Female
Fibroblasts / drug effects*
Fibroblasts / pathology
Fluoroquinolones / chemistry
HL-60 Cells
HeLa Cells
Humans
Immunologic Factors / chemical synthesis
Immunologic Factors / pharmacology*
Melanoma / drug therapy*
Melanoma / pathology
Melanoma, Experimental
Mice
NIH 3T3 Cells
Quinolines / chemical synthesis
Quinolines / pharmacology*
Quinolones / chemical synthesis
Quinolones / pharmacology*
RAW 264.7 Cells
Uterine Cervical Neoplasms / drug therapy*
Uterine Cervical Neoplasms / pathology

Substances

1,4-dihydroquinoline
Antineoplastic Agents
Cytokines
Fluoroquinolones
Immunologic Factors
Quinolines
Quinolones
fluoroquinolone ethyl 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
Caspase 9