The study of cytotoxic/toxic effect of selenadiazoloquinolone derivative on viability and morphology of fibroblast cells and 3D tissue model
Michaela Janošková 1
Viktor Milata 2
Soňa Jantová 1
1 Ústav biochémie a mikrobiológie, Fakulta chemickej a potravinárskej technológie STU v Bratislave, Bratislava, Slovenská republika 2 Oddelenie organickej chémie, Fakulta chemickej a potravinárskej technológie STU v Bratislave, Bratislava, Slovenská republika
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4-Quinolones (4-oxoquinolines) represent a group of heterocyclic compounds known for tithes of years, many of which are currently used worldwide in the medical practice (e.g., ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin). Quinolone derivatives are multitarget agents with a variety of biological activities. They have been demonstrated to possess antitumor and immunomodulatory activities, too (1,2). Some of them have been developed for clinical use in human medicine. Several of quinolone derivatives currently being explored in the clinic as potential drug for different hematologic malignancies or acute myeloid leukemia therapy.
Based on the reported effects of quinolone derivatives, a new series of substituted selenadiazoloquinolones, were prepared by Bella et al. (3) and derivatives were screened for photochemical, antimicrobial and cytotoxic/phototoxic activities in vitro. Some of them demontrated biological activity. The highest cytotoxicity/phototoxicity on the selected cancer cell lines exhibited non-photoactivated and photoactivated 7-acetyl- 6,9-dihydro-6-oxo-[1,2,5]selenadiazolo[3,4-h] quinoline (derivative E2h). Derivative E2h induced apoptotic death of cancer cell lines HeLa and HL-60. Biological and EPR studies demontrated that E2h behave as photosensitizers activating molecular oxygen upon photoexcitation and possess the sufficient photochemical stability under the given experimental conditions (4,5).
The aim of the present study was to examine toxicity of selenadiazoloquinolone derivative E2h on human non-cancer fibroblast BHNF-1 cells and reconstructed human epidermis tissues EpiDermTM. Further E2h effects on tissue structure and morphology was observed.
Derivative E2h induced on non-cancer BHNF-1 cells relative low antiproliferative effect, which even decreased with the time of influence. The cytotoxicity of the highest tested concentration of E2h was only 25.2%, after 72 h of treatment.
3-D human skin culture (EpiDermTM) is a living reconstituted human epidermis used to provide information regarding the cytotoxicity, irritant potential and immunotoxicity of different compounds. In our study, we used this 3D skin model for observation of E2h toxicity. Toxicity studies showed that selenadiazoloquinolone E2h did not manifested toxic effect, percent of cell viability was in the range 95-100.
EpiDermTM (MatTek, Slovakia) is a multilayered, differentiated tissue consisting of basal, spinous, granular and cornified layers resembling the normal human epidermis. The tissue is constructed from normal epidermal keratinocytes (foreskin-derived), which are cultured on chemically modified, collagen-coated, 9-mm (i.d.) cell culture inserts (e.g. Millicell CM or Nunc polycarbonate cell-culture inserts). Morphological and histological examination showned that the control tissue and tissue treated with E2h concentration of 143 µM consisted non-damage layers and none structural and morphological changes were found.
In summary, we can conclude that anticancer active 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5] selenadiazolo [3,4-h]quinoline-7-carboxylate (E2h) induce a low antiproliferative activity on fibroblast BHNF-1 cells and is no toxic on three-dimensional skin constructs EpiDerm™. It can be included to potent non-toxic drug with anticancer potential.
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