INTRODUCTION: A number of biochemical and medical researchers have detected increased activity of tyrosinase in skin tumor cells. The most famous and available inhibitor, kojic acid, has several side effects and is not completely safe for use. OBJECTIVES: This paper describes the study of inhibitory influence of halogen boroxine K 2 [B 3 0 3 F 4 OH] on tyrosinase. The research was prompted by the ability of this compound to inhibit enzymes through metal ion chelation as well as its synthesis and application in cosmetic skin products that produce no serious side-effects. METHOD: Tyrosinase activity was measured by spectrophotometric analysis for the appearance of dopachrome pigment at a wavelength of 475 nm. Tyrosinase exhibited typical Michaelis-Menten kinetics. RESULTS: Tests of the proposed inhibition of the enzyme tyrosinase showed that K 2 [B 3 O 3 F 4 OH] had weak inhibitory properties. CONCLUSION: It will be necessary to search for new ways of antitumor mechanisms that differ from those of previous results.

Abstract The effect of Ca2+ ions on the cytotoxic ability of boron heterocyclic compound dipotassium-trioxohydroxytetrafluorotriborate (K2[B3O3F4OH]), on in vitro tumor cells (mammary adenocarcinoma 4T1, melanoma B16F10 and squamous cell carcinoma SCCVII) and non-tumoral fibroblast cells (mouse dermal L929 and hamster lung V79) was examined. At small concentrations of Ca2+ ions (0.42 mM), K2[B3O3F4OH] (3.85 mM) has a very strong cytotoxic effect on all cancer cells tested (89.1, 85.6 and 84.6%) and significantly less effect on normal cells (19.5 and 24.2%), respectively. Applying larger concentrations of Ca2+ ions (9.42–72.42 mM), at the same concentration of K2[B3O3F4OH], no significant cytotoxic effect was detected on cancer cells and normal cells investigated. The selective ability of K2[B3O3F4OH], in the medium with a low concentration of Ca2+ ions has a strong cytotoxic effect on cancer cells and very weak effect in normal cells, opens up the possibility of its application in antitumor therapy.

Genotoxic effects of inorganic molecule dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), a promising new therapeutic for the epidermal changes treatment, have been evaluated. In vitro analysis included evaluation of genotoxic and cytotoxic potential of K2(B3O3F4OH) in concentrations of 0.01, 0.02, 0.05 and 0.06 mg/mL applying cytokinesis-block micronucleus cytome assay in human lymphocyte culture. With the increase of concentration the frequency of micronuclei elevated but the differences were not significant. Also, there were no significant differences among the frequencies of nuclear buds and nucleoplasmic bridges between controls and treated cultures. Nuclear division index and nuclear division cytotoxycity index values did not reveal significant cytotoxic effect of K2(B3O3F4OH). In vivo genotoxic effects were analyzed on BALB/c mice applying reticulocytes micronucleus assay. K2(B3O3F4OH) was administrated intraperitoneally in final concentrations of 10, 20, 50 and 55 mg/kg. Significant decrease of reticulocytes ratio and increase of micronuclei frequencies against pre-treatments were found for both sampling periods of 48 and 72 hours of the highest applied concentration. This study confirmed that K2(B3O3F4OH) is not genotoxic in tested concentrations in vitro as well as in concentrations lower than 55 mg/kg in vivo. This study presents a reliable basis for further pre-clinical and potential clinical investigations.

s submitted to the 41st FEBS Congress, which was planned for Kuşadası, Turkey from 3rd to 8th September 2016, and accepted by the Congress Organizing Committee are published in this Special Issue of The FEBS Journal. Unfortunately, the Congress was cancelled by FEBS after the excellent scientific programme was compromised by an insufficient number of confirmed speakers, and so the authors of these abstracts were not able to present their work at the event*. Late-breaking abstracts and abstracts withdrawn after Congress cancellation are not included in this issue. About these abstracts Abstracts submitted to the Congress are not peer-reviewed. In addition, abstracts are published as submitted and are not copyedited prior to publication. We are unable to make corrections of any kind to the abstracts once they are published. Indexing Abstracts published in The FEBS Journal Special Issue for the 41st FEBS Congress will be included individually in the Conference Proceedings Citation Index published by Web of Science. How to cite these abstracts AuthorOne, A., AuthorTwo, B. (2016). Abstract title. FEBS J, 283: Abstract number**. doi:10.1111/febs.13903 * An optional closed online presentation opportunity of short duration on the Congress website was offered after Congress cancellation and may be taken up by some abstract authors. ** Each abstract has been given a unique number beginning with either the letters P or ST; the next part relates to the session in which the speed talk or poster will be presented. 01.02 RNA biology, biogenesis and processing 02.03 Autophagy: Regulation mechanisms 02.04 Mechanisms and regulation of protein translocation 02.05 Intracellular organization 02.06 Human microbiome (microbiota) 02.07 Extracellular matrix and metalloproteinases 09.04 Chemical and biochemical aspects of oxidative stress Mis Miscellaneous 428 The FEBS Journal 283 (Suppl. 1) (2016) 428 DOI: 10.1111/febs.13903 © 2016 The Authors. The FEBS Journal © 2016 FEBS This addendum corrects errors in the Speed Talks and Poster sessions of the Supplement S1. The following abstracts were omitted by mistake from the original line-up. In addition, the abstracts P-02.03.3-002 and P-09.04.4-104 were truncated in the original document and are reproduced in full here. FEBS_v283_s1_13903.indd 1 10/12/2016 2:00:46 PM OMITTED POSTER SESSIONS Tuesday 6 September 12:30–14:30 Autophagy: Regulation mechanisms P-02.03.3-002 Apoptotic and necrotic effects of low dose bisphenol A in SHSY5Y neuroblastoma cells B. Ayazg€ok, T. T€ uyl€ u K€ uc € ukkilinc Hacettepe University Faculty of Pharmacy, Ankara, Turkey Bisphenol A (BPA) is a commonly used chemical in industry to make plastics. “Low-dose” term has been expressed for the first time in studies with BPA in 2001. The value of low dose was received as <1 lM for BPA in in vitro studies. Nowadays majority of the population as a result of today’s lifestyle exposured to low doses BPA chronically, thus importance of low-dose toxicity studies is revealed. In this study we aimed to examine cytotoxicity composed by low dose BPA in SHSY5Y cells in terms of appoptotic and necrotic effects.SHSY5Y cells was seeded at 300.000 cells per well in 6-well plates and cultured in DMEM at 37°C with 5% CO2.SH-SY5Y cells were treated with low dose(1 pM, 1 nM) of BPA. Plate was incubated for 24 and 48 hours. After the incubation period, samples were pooled then washed with PBS in two times and 100 ll aliquot of cells from each sample was centrifuged at 12000 g, +4 °C for 2 minutes and resuspended in 100 ll annexin binding buffer added to 5 ll Annexin V and incubated at room temperature in the dark for 20 minutes. Then, samples were centrifuged and resuspended again in 100 ll of the same buffer and added with 1 ll PI at room temperature for 1–4 minutes and analysed at Tali Image-Based Cytometer. Reducing cell viability of low dose BPA in SHSY5Y neuroblastoma cells is revealed by MTT by our group in our previous studies. Cytotoxicity studies are conducted for 1 pm and 1 nm of BPA in 48 hours by taking into account this result. It is obtained that 1pM reduced cell viability to % 63 and 1 nM BPA decreased cell viability to %78. It is clearly ocuured via examinate of necrotic effects that group treated with 1 pM and 1 nM BPA was significiantly different from control group. It has observed group treated with 1 pM and 1 nM BPA has importantly difference compared control group. The findings obtained from this study explain the cytotoxicity of BPA in SHSY5Y cells through necrotic and late apoptotic pathways. P-02.03.3-005 Lack of Atg5 expression diminished apoptotic potential of cdk inhibitors due to increased Bcl-2 expression in MEF cells A. E. Nezir, E. D. Arisan, A. Coker-Gurkan, P. Obakan,

The boron heterocyclic compound dipottasium trioxohydroxytetraflourotriborate, K2[B3O3F4OH] has been listed as a promising new therapeutic for the epidermal changes treatment. In order to elucidate its free radical scavenging activity, several appropriate thermodynamic molecular descriptors were calculated with the help of quantum-chemistry methods and their values were compared with the data obtained for ascorbic acid, trimethlyboroxine and trimethoxyboroxine. Considering the results, it may be suggested that the single electron transfer followed by proton transfer (SET-PT) is more favourable reaction pathway than hydrogen atom transfer (HAT) for the halogenated boroxine K2[B3O3F4OH]. Experimental support is provided by evaluating the in-vitro antioxidant activity of the investigated compounds in terms of their ferric-reducing antioxidant power (FRAP). Our study reveals that all three examined boroxines are extremely weak antioxidants.

Abstract Dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was listed as a promising new therapeutic for cancer diseases. For in vitro and in vivo investigation of its antitumor effects 4T1 mammary adenocarcinoma, B16F10 melanoma and squamous cell carcinoma SCCVII were used. The detailed in vitro investigation undoubtedly showed that K2[B3O3F4OH] affects the growth of cancer cells. The proliferation of cells depends on the concentration so that aqueous solution of K2[B3O3F4OH], the concentrations of 10−4 M and less, does not affect cell growth, but the concentrations of 10−3 M or more, significantly slows cells growth. B16F10 and SCCVII cells show higher sensitivity to the cytotoxic effects of K2[B3O3F4OH] compared to 4T1 cells. Under in vivo conditions, K2[B3O3F4OH] slows the growth of all three tumors tested compared to the control, and the inhibitory effect was most pronounced during the application of the substance. There is almost no difference if K2[B3O3F4OH] was applied intraperitoneally, intratumor, peroral or as ointment. Addition of 5-FU did not further increase the antitumor efficacy of K2[B3O3F4OH].

Abstract The genotoxicity of halogenated boroxine [K2(B3O3F4OH)], a novel compound with the potential for prevention and/or treatment of various skin changes, has been confirmed in human lymphocytes. The potential of luteolin and delphinidin in inhibition of the genotoxic and cytotoxic effects of halogenated boroxine in vitro was analyzed applying the chromosome aberration analysis and the cytokinesis-block micronucleus cytome assay in human lymphocyte cultures. The in vitro treatments included addition of boroxine and flavonoids independently, and combined treatments of boroxine with luteolin or delphinidin. In the concentration of 50 μM, luteolin significantly decreased the frequency of micronuclei and nuclear buds. Delphinidin suppressed the occurrence of aberrant cells in the presence of the halogenated boroxine, but also affected their induction in respective delphinidin treatment. Detection of endoreduplications in combined treatments indicated that these flavonoids are potential inhibitors of cell cycle or topoisomerase II activity. The obtained results have confirmed antigenotoxic activity of selected bioflavonoids in vitro. The side effects of potential therapeutic applications of halogenated boroxine may be inhibited in the presence of bioflavonoids in appropriate dosage.

Abstract The boron heterocyclic compound dipotassium-trioxohydroxytetrafluorotriborate (K2[B3O3F4OH]) was investigated as inhibitor of the zinc enzyme, carbonic anhydrase (CA, EC 4.2.1.1). Eleven human (h) CA isoforms, hCA I–IV, VA, VI, VII, IX and XII–XIV, were included in the investigations. The anion, similar to tetraborate or phenylboronic acid, inhibited most of them. hCA III was not inhibited by K2[B3O3F4OH], whereas hCA VA, hCA VI, hCA IX and hCA XIII were inhibited in the submillimolar range, with KIs of 0.31–0.63 mM. hCA I and II (cytosolic, widespread isoforms), hCA IV (membrane-bound isoform), hCA XII (tumor-associated, transmembrane) and hCA XIV (transmembrane) were much more effectively inhibited by this anion, with inhibition constants ranging from 25 to 93 µM. hCA VII, a cytosolic enzyme present in the brain and associated to oxidative stress, was very effectively inhibited by K2[B3O3F4OH], with a KI of 8.0 µM. We propose that K2[B3O3F4OH] binds to the metal ion from the enzyme active site, coordinating to the Zn(II) ion monodentately through its B-OH functionality. We hypothesize that some of the beneficial antitumor effects reported for K2[B3O3F4OH] may be due to the inhibition of CAs present in skin tumors.

Abstract In the development of boronic acid-based enzyme inhibitors as potential pharmaceutical drugs, dipotassium trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was listed as a promising new therapeutic for treatment of these diseases. The catalase-mediated conversion of hydrogen peroxide, in the presence and absence of K2[B3O3F4OH] was studied. The kinetics conformed to the Michaelis–Menten model. Lineweaver–Burk plots were linear and plotted the family of straight lines intersected on the abscissa indicating non-competitive inhibition of the catalase. It appears that in the absence of inhibitor, catalase operates the best at conditions around pH 7.1 and in the presence of K2[B3O3F4OH] the optimum is around pH 6.2. The uncatalyzed reaction of hydrogen peroxide decomposition generally has a value of activation energy of 75 kJ mole−1, whereas catalase, in the absence of inhibitor, lowers the value to 11.2 kJ mole−1, while in the presence 69 mmoles L−1 of K2[B3O3F4OH] it was 37.8 kJ mole−1.

Alzheimer's is a disease that causes dementia disorders. Alzheimer's dementia is the most common form of dementia in modern society (affects more than 20 million people around the world). Currently, the only effective treatment for Alzheimer’s disease (AD) targets the cholinergic system using inhibitors of cholinesterase (ChE). Since only a small number of drugs for treatment of AD cognitive dysfunction and memory loss associated with AD (a few synthetic medicines, e.g. tacrine, donepezil and the natural product- based rivastigmin and galanthamine) exist, there is a great interest in finding new ChE inhibitors. Butyrylcholinesterase is an enzyme that acts as a natural "cleaner" compounds which inhibit acetylcholinesterase. It is possible that the various changes associated with cholinergic synapses and neurons and glial cells, increased in the brain in Alzheimer's disease suggests that the inhibition of BuChE (compared to AChE) could be more important in the progression of Alzheimer's disease.

We have examined antiproliferative, cytotoxic, and genotoxic potential of a halogenated boroxine dipotassium trioxohydroxytetrafluorotriborate [K2(B3O3F4OH)]. The impact on cell growth was evaluated by alamarBlue assay in basal cell carcinoma culture. Cytostatic, cytotoxic, and genotoxic potential were evaluated in lymphocytes culture, applying cytokinesis-block micronucleus cytome assay and chromosome aberrations analysis. Tested concentrations (0.05, 0.1, 0.2, and 0.4 mg/mL) were correlated with inhibition of cell growth in basal cell carcinoma culture and with the lymphocytes proliferation. Clastogenic activity has been confirmed, without evidences of aneugenic activity, in human lymphocytes.