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  • Author: Soňa Jantová x
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ABSTRACT

Natural essential oils are volatile herbal complex compounds which manifest cytotoxic effects on living cells depending on their type and concentration but usually they are not genotoxic. Our previous studies showed that carvacrol (CA) and rosemary essential oil (RO) induced growth inhibition of both human cell lines HepG2 and BHNF-1, with hepatoma HepG2 cells being more sensitive to either compound tested. Cytotoxic concentrations of CA and RO induced the formation of DNA strand breaks. Further ex vivo studies showed that extracts prepared from hepatocytes of CA- and RO-supplemented rats did not increase incision repair activity compared to extracts from liver cells of control animals. Therefore, the aim of this work was to determine the effect of cytotoxic concentrations of CA and RO on the cell cycle and the ability of both natural volatiles to induce DNA fragmentation and apoptotic death of human hepatoma HepG2 cells. These effects were measured after 24 h incubation of HepG2 cells with CA and RO using three independent methods - flow cytometry, internucleosomal DNA fragmentation (electrophoresis) and micronucleus assay. Evaluation of morphological changes and formation of micronuclei in HepG2 cells showed no increase in the number of micronuclei in cells treated by CA and RO compared to control cells. On the other hand, CA and RO induced morphological changes typical for apoptosis in concentration-dependent manner. The presence of necrosis was negligible. Both natural compounds caused shrinking of cytoplasmic membrane and formation of apoptotic bodies. In addition, the highest concentrations of CA and RO induced internucleosomal DNA fragmentation (formation of DNA ladder) in HepG2 cells. Cell cycle analysis revealed the accumulation of cells in the G1 phase, which was accompanied by a reduction in the number of cells in the S phase after 24 h exposure to the substances tested. The cell division was thus slowed down or stopped and this process resulted in cell death

Abstract

The new synthetically prepared quinolone derivative 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo [3,4-h]quinoline-7-carboxylate (E2h) showed in our previous study cytotoxic effects towards tumor cells and immunomodulatory activities on RAW 264.7 cell line murine macrophages. E2h may have a potential use as a novel chemotherapeutic agent with immunomodulatory properties and the ability to induce apoptotic death of cancer cells. The aim of the present study was to examine the antiproliferative/cytotoxic activities of E2h on human non-cancer fibroblast BHNF-1 cells and reconstructed human epidermis EpiDerm™. Further the effects of E2h on tissue structure and morphology were examined. Cytotoxic/toxic studies showed that selenadiazoloquinolone is not toxic on normal human fibroblast cells BHNF-1 and dimensional skin constructs EpiDerm™. Evaluation of morphological changes in EpiDerm™ showed no change in the construction and morphology of skin tissue treated by E2h compared to control.

ABSTRACT

Salvia officinalis, L. (Lamiaceae) is one of the most widespread herbal species used in the area of human health and in the foodprocessing industry. Salvia and its extracts are known to be a rich source of antioxidants. As shown previously, the crude ethanolic extract of salvia (SE) exerts lower anti-oxidative properties in lard compared to the new salvia food formulations No. 1 (SF1; 32% of SE + 68% of the emulsifier Dimodan S-T) and No. 2 (SF2; 32% of SE + 68% of the emulsifier Topcithin 50).

The aim of the present study was to investigate and compare the effects of the SE and its food formulations SF1 and SF2 on the toxicity and/or proliferation of L1210 leukemia cells. We found that SE and both SF1 and SF2 demonstrated different concentration- and time-dependent cytotoxic/antiproliferative cellular effects already within the first 24 h of the treatment. However, SE was nearly 10 times more effective than the new salvia food formulations SF1 and SF2.

We investigated partially also the molecular mechanisms lying behind the action of SE, SF1 and SF2 induced apoptosis in our cell model. We found an apparent involvement of the mitochondrial/caspase-dependent pathway in the described processes. Nevertheless, further investigation is needed before salvia extract and its new antioxidant formulations can be included among the potential food antioxidants with protective properties against cancer.

ABSTRACT

Quercetin is a natural polyphenol with proven health beneficial activities. In this study 15 new quercetin derivatives were prepared with the aim to enhance their bioavailability. Modification of their physicochemical properties could herewith improve the action in cells. The prepared compounds were tested for their antioxidant and cytotoxic activity. The ability to scavenge free radicals as well as ferric reducing antioxidant power of the new derivatives was not better than that of unmodified quercetin. But for acetylated esters a better cytotoxic activity was found on human cervical cancer cells HeLa than for the initial molecule. The best effect revealed chloronaphtoquinone quercetin (IC50=13.2 μM). For this compound comparable cytotoxic action on non-cancer murine fibroblast cells was detected (IC50=16.5 μM). The obtained results indicate that appropriate lipophilization of the quercetin molecule could improve its cytotoxic action in cells, probably due to its enhanced bioavailability