Renata Kontek

Antioxidant enzymes activity and phenolic compounds content in red cabbage seedlings exposed to copper stress.

The phenolics: anthocyanin (ATH), sinapoyl esters and activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POX), ascorbate peroxidase (APX), glutathione peroxidase (GPX) and glutathione reductase (GR), in red cabbage seedlings subjected to Cu2+ stress were investigated. Cu2+ at low doses (0.5 mM), increased the levels of ATH and sinapoyl derivatives in red cabbage. High Cu2+ concentration (2.5 mM) provoked oxidative stress and enhanced thiobarbituric acid reactive substances (TBARS) content in tissues. A lower level of TBARS was correlated with high ATH content. It seems that synthesis of these isoflavonoids is an effective strategy against reactive oxygen species (ROS). The analysis of the antioxidant enzymes activity suggested that peroxidases were the most active enzymes in red cabbage seedlings exposed to Cu2+ stress. It could results from the fact that phenolic compounds (PhC), which could be also substrates for different peroxidases, were the first line of defence against metal stress.

Red cabbage anthocyanin extract alleviates copper-induced cytological disturbances in plant meristematic tissue and human lymphocytes

Red cabbage is a source of health beneficial substances with antioxidant and antigenotoxic properties. HPLC analysis specifying the content of the investigated extract indicated that mainly anthocyanins (ATH) were responsible for its abilities. Cytological research was conducted with two experimental models: plant tissues—meristematic cells of Vicia faba, and animal tissue elements—human lymphocytes. Positive influence of ATH extract on mitotic activity of Vicia cells exposed to Cu2+ stress, and inhibitory effect of ATH on cytotoxic actions of Cu2+ on lymphocytes were demonstrated. In all experimental series with ATH application in combinations with Cu2+, mitotic index (MI) were higher than those obtained for only Cu2+ stressed tissues. Preincubation in ATH before Cu2+ stress had the best effect. Similarly, after ATH applications in all tested series decrease in frequency of micronuclei (MN) appearance was noticed in comparison with only Cu2+ stressed material. In the case of Vicia cells ATH acted effectively even applied after Cu2+ stress. It suggests that this ATH mixture not only prevents and limits but also heals the cytological injury caused by Cu2+ stress.

The modulatory effect of melatonin on genotoxicity of irinotecan in healthy human lymphocytes and cancer cells.

Drug-target interactions can be modified by adding modulatory agents to increase treatment efficacy and clinical outcome. Combination chemotherapy has become increasingly important because drugs acting synergistically can achieve therapeutic effects at substantially lower doses and with a limited spectrum of side effects. Irinotecan, known as one of the camptothecin analogs, has shown a broad spectrum of antitumor activity against various malignancies. In this study, we evaluated the effect of melatonin on the genotoxic activity of irinotecan in healthy human lymphocytes and a lung cancer cell line (A549) and a colorectal adenocarcinoma cell line (HT29) in vitro. Irinotecan, as a single agent, was shown to induce DNA damage in all types of analyzed cells. The combination of melatonin at concentrations of 50 μM with increasing doses of irinotecan (7.5, 15, 30, and 60 μM) resulted in an increase in the amount of DNA damage in A549 and HT29 cancer cells, but was not effective in inducing DNA damage in healthy human lymphocytes. Analysis of the efficacy of DNA repair, performed after 60 and 120 minutes of postincubation, showed the gradual decrease of DNA percentage in comet tails during repair postincubation in all experimental samples. Our results indicate that melatonin can modulate the genotoxic activity of irinotecan and DNA repair efficacy in human cancer cells in vitro. These findings may be supportive for the optimization of therapeutic efficacy in irinotecan treatment.

The antioxidants, vitamin A and E but not vitamin C and melatonin enhance the proapoptotic effects of irinotecan in cancer cells in vitro

Irinotecan is one of the camptothecin analog which has been shown to have a broad spectrum of antitumor activities against various malignancies. The aim of this study was to evaluate the effect of vitamin A, C, E and melatonin on proapoptotic activity of irinotecan in human cancer cells in vitro. We observed that irinotecan induced apoptosis in all types of analyzed cell lines when used as a single agent. Combination of selected antioxidants with various doses of irinotecan (7.5-60μM) resulted in significant increase in apoptotic cell death in A549 and HT29 cancer cell lines. The highest killing efficiency was observed after co-incubation of the cells with irinotecan and vitamin A (10μM), or vitamin E (25μM), respectively. The addition of vitamin C and melatonin to irinotecan treatment did not promote increase in killing of cancer cells. Our results indicate that some antioxidants can enhance the proapoptoic activity (properties) of irinotecan in human cancer cells in vitro. These findings may be supportive for the optimization of therapeutic efficacy of irinotecan treatment.

Red cabbage extract limits copper stress injury in meristematic cells of Vicia faba

Natural phenolic compounds (phenolic acids, flavonoids, tannins, lignans) present in food of plant origin are in the focus of interest due to their prevalence, properties and biological activity. The aim of the presented work was to investigate antioxidant and antigenotoxic effects of the anthocyanin-rich extract from red cabbage leaves (Brassica oleracea rubrum) on the changes induced by toxic Cu2+ concentrations. MeOH extract from red cabbage containing anthocyanin (ATH) and phenolic acid derivatives exhibited strong antioxidant properties. Cu2+ decreased mitotic index (MI) and inhibited proliferative activity of Vicia faba root meristematic cells. The morphology of mitotic chromosomes was changed; “erosion” and pulverization might result from Cu2+ high-cytotoxicity. Numerous micronuclei, chromatid bridges and lagging/lost chromosomes were found in the meristematic cells of V. faba, which indicate the clastogenic effect of Cu2+. The application of the ATH-rich extract lowered the number of disturbances induced by Cu2+. The positive role of the ATH-rich red cabbage extract will be discussed.

Genotoxic effects of irinotecan combined with the novel platinum(II) complexes in human cancer cells.

Combination chemotherapy has become increasingly important as synergistic drugs enable to achieve therapeutic effects at substantially lower doses and limited spectrum of side effects. Irinotecan as a one of the camptothecin analogues has shown a broad spectrum of antitumor activity against various malignancies. It is commonly used in treatment of gastrointestinal and pulmonary cancer. In this study were measured the effect of the novel platinum(II) complexes: cis-[PtCl(2)(4-pmOpe)(2)] and trans-[PtCl(2)(4-pmOpe)(2)], with diethyl (pyridine-4-ylmethyl)phosphates (4-pmOpe) as non-leaving ligands, on genotoxicity of irinotecan in human cancer cells. Irinotecan showed genotoxic activity in combination with the new platinum(II) derivatives in cancer cells. Combination of irinotecan with cis-[PtCl(2)(4-pmOpe)(2)] or trans-[PtCl(2)(4-pmOpe)(2)] resulted in significant increase in DNA damage in A549 and HT29 cells when compared to effects of irinotecan or platinum(II) complexes used separately. The highest degree of DNA migration in the comet tails was found after the cancer cells were treated with irinotecan and trans-[PtCl(2)(4-pmOpe)(2)]. In addition, the analysis of DNA repair revealed that irinotecan in combination with trans-[PtCl(2)(4-pmOpe)(2)] induced unrepairable DNA damage suggesting the poor recognition of the damage by HMG proteins and other repair mechanisms. Thus, genotoxicity of irinotecan was modulated by the structurally different DNA-platinum adducts formed by novel platinum(II) complexes. These data suggest that the use of irinotecan with novel platinum(II) complexes may represent a new strategy for pharmacotherapy in cancer.

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

Summary A large series of variously substituted amino(pyren-1-yl)methylphosphonic acid derivatives was synthesized using a modified aza-Pudovik reaction in 20–97% yields. The fluorescence properties of the obtained compounds were investigated revealing that N-alkylamino(pyren-1-yl)methylphosphonic derivatives are stronger emissive compounds than the corresponding N-aryl derivatives. N-Benzylamino(pyren-1-yl)methylphosphonic acid displayed strong fluorescence (ΦF = 0.68) in phosphate-buffered saline (PBS). The influence of a series of derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 μM), simultaneously showing weak toxicity towards normal lymphocytes (IC50 = 230.8 µM).

Synthesis and biological evaluation of some amino- and sulfanyl-3H-quinazolin-4-one derivatives as potential anticancer agents

A series of 6-substituted quinazolinone derivatives were prepared by the reaction of 6-bromoquinazolinones with aryl or alkyl amines and thiols, in the presence of a Pd(OAc)2/Xantphos system, under Buchwald–Hartwig-type reaction conditions. The 6-bromoquinazolinones were obtained in the three-components reaction of 5-bromoisatoic anhydride, triethyl orthoformate and an appropriate amine. Biological screening of the potential cytotoxicity of synthesized compounds on HT29 and HCT116 cell lines, as well as on the lymphocytes, showed that some derivatives of quinazolinone have significant anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported.Graphical abstract

Triterpenoid components from oak heartwood (Quercus robur) and their potential health benefits

For centuries oak wood (Quercus robur) has been used in aging of wines and spirits, which is based on pleasant flavors given to beverages by phenolics transferred to the liquid during the maturation process. Other metabolites, such as triterpenoids, can also be released. Searching for extractable triterpenoids in oak heartwood, 12 new, 1-12, and five known, 13-17, oleanane types were isolated and characterized. Their cytotoxicities were tested against cancer cells (PC3 and MCF-7) and lymphocytes. Breast cancer cells (MCF-7) were the most affected by triterpenoids, with roburgenic acid, 4, being the most active compound (IC50 = 19.7 μM). Selectivity was observed for compounds 1-3, 8, 9, and 16, exhibiting an IC50 > 200 μM against lymphocytes, while active against cancer cells. A galloyl unit attached to the triterpenoid moiety was established as the key feature for such effect. These results highlight the occurrence of triterpenoids in oak heartwood and their relevance for chemoprevention of breast cancer.