The dicyano compound induces autophagic or apoptotic cell death via Twist/c-Myc axis depending on metastatic characteristics of breast cancer cells.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease with various subtypes, therefore, the illumination of distinctive mechanisms between subtypes for the development of novel treatment strategies is important. Here, we revealed the antiproliferative effects of our customized dicyano compound (DC) on BC cells. METHODS AND RESULTS: We determined the antiproliferative effect of the DC on non-metastatic MCF-7 and metastatic MDA-MB-231 cell lines by MTT. We evaluated protein levels of LC3BI-II and p62 to detect effects of the DC on autophagy. Furthermore, we examined whether the DC induce apoptosis in MCF-7 and MDA-MB-231 cells by performing TUNEL and western blotting. We showed that the DC induces autophagic cell death in MDA-MB-231 while it leads to apoptosis in MCF-7, demonstrating that DC can induce different cell death mechanisms in BC cells according to what they represent subtypes. To understand the reason of different cell response to the DC, we evaluated the expressions of several regulator proteins involved in survival, cell arrest and proliferation. All findings revealed that c-Myc expression is directly correlated with autophagy induction in BC cells and it could be a marker for the selection of cell death mechanism against anti-cancer drugs. Interestingly, we showed that the overexpression of Twist, responsible for metastatic features of BC cells, imitates the effects of autophagy on c-Myc expression in MCF-7 cells, indicating that it is implicated in both the regulation of c-Myc as a upstream factor and subsequently the selection of cell death mechanisms. CONCLUSION: Taken together, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in BC subtypes with different invasive characteristics.

Novel nonperipheral octa-3-hydroxypropylthio substituted metallo-phthalocyanines: synthesis, characterization, and investigation of their electrochemical, photochemical and computational properties.

The current study describes the synthesis, electrochemical, computational, and photochemical properties of octa (3-hydroxypropylthio) substituted cobalt (II) ( 4 ), copper (II) ( 5 ), nickel (II) ( 6 ) and zinc(II) ( 7 ) phthalocyanine derivatives. These novel compounds were characterized by elemental analysis,1H,13C NMR, FT-IR, UV-Vis, and MS. The redox behaviors of these metallo-phthalocyanines were investigated by the cyclic voltammetric method. The optimized molecular structure and gauge-including atomic orbital (GIAO)1H and13C NMR chemical shift values of these phthalocyanines in the ground state had been calculated by using B3LYP/6-31G(d,p) basis set. The outcomes of the optimized molecular structure were given and compared with the experimental NMR values. The photochemical properties including photodegradation and singlet oxygen generation of zinc(II) phthalocyanine were studied in DMSO solution for the determination of its photosensitizer behaviors.

The triazole linked galactose substituted dicyano compound can induce autophagy in NSCLC cell lines.

As seen in other types of cancer, development of drug resistance in NSCLC treatment causes adverse effects on disease fighting process. Recent studies have shown that one of the drug resistance development mechanisms is that cancer cells may acquire the ability to escape from cell death. Therefore, development of anticancer drugs which have the strategy to redirect cancer cells to any cell death pathways may provide positive results for cancer treatments. Autophagy may be a target mechanism of alternative cancer treatment strategy in cases of blocked apoptosis. There is also a complex molecular link between autophagy and apoptosis, has not been fully understood yet. The dicyano compound which we used in our study caused cell death in NSCLC cell lines. When we analyzed the cells which were treated with dicyano compound by transmission electron microscope, we observed autophagosome structures. Upon this result, we investigated expression levels of autophagic proteins in the dicyano compound-treated cells by immunoblotting and observed that expression levels of autophagic proteins were increased significantly. The TUNEL assay and qRT-PCR for pro-apoptotic and anti-apoptotic gene expression, which we performed to assess apoptosis in the dicyano compound-treated cells, showed that the cell death does not occur through apoptotic pathway. We showed that the dicyano compound, which was developed in our laboratories, may play a role in molecular link between apoptosis and autophagy and may shed light on development of new anticancer treatment strategies.

Comparative Investigation of Peripheral and Nonperipheral Zinc Phthalocyanine-Based Polycarbazoles in Terms of Optical, Electrical, and Sensing Properties.

In this study, nonperipherally alkyl-linked carbazole conjugated novel zinc(II) phthalocyanine was synthesized by cyclotetramerization reaction of 6-(9 H-carbazol-9-yl)hexane-1-thiol and 3,6-bis(tosyloxy) phthalonitrile in a one-step reaction. Optical, electrical, and sensing properties of this super structured polycarbazole obtained by electropolymerization are compared with peripherally alkyl-linked polycarbazole-based zinc(II) phthalocyanine. It has been found that the attachment of alkyl-linked carbazoles to the phthalocyanine molecule in either peripheral or nonperipheral positions has a great effect on the optical and electrical properties and sensing ability of the resulting polycarbazole derivatives. P(n-ZnPc) has the highest electrochromic contrast (70.5%) among the derivatives of zinc(II) phthalocyanines in the literature. In addition to these, the sensor platform has been successfully established, and analytical optimizations have been carried out. When the sensors prepared with zinc(II) phthalocyanine are examined, it was specified that the n-ZnPc- co-TP/GOx was ranked first in the literature with high sensor response and stability. As a result, by changing of the peripheral and nonperipheral position of phthalocyanines, their physical properties can be tuned to meet the requirements of desired technological application.

Zinc(II) phthalocyanine fused in peripheral positions octa-substituted with alkyl linked carbazole: Synthesis, electropolymerization and its electro-optic and biosensor applications.

Zinc(II) phthalocyanine fused in peripheral positions octa-substituted with alkyl linked carbazole has been prepared by cyclomerization reaction of 4,5-bis(6-carbazole-9-yl-hexylsulfanil)phthalonitrile in the presence of anhydro Zn(II) acetate and a strong organic base (DBU). Synthesis steps were optimized and higher efficiency synthesis was achieved. The purpose of combining of carbazole moieties with phthalocyanine on the peripheral position is to enhance some properties such as photo and electrochemical properties because of strong electron-donating properties of carbazole group. This molecule has been electrochemically polymerized and the electrical and optical properties of the resulting conductive polymer have been investigated. Amperometric detection was carried out following oxygen consumption at -0.7V vs. the Ag reference electrode in phosphate buffer (50mM, pH 6.0). The novel biosensor showed a linear amperometric response for glucose within a concentration range of 0.05mM to 1.5mM (LOD: 0.024mM). This result shows that modification of the proposed biosensor by copolymerization have provided to give perfect response to different glucose concentrations. Because of its superior spectral and electrochemical properties and contained zinc metal which can act as a mediator during biochemical reactions, this material has been used as a glucose biosensor platform to detection for real samples.

ATR-FTIR Spectroscopy Highlights the Problem of Distinguishing Between Exophiala dermatitidis and E. phaeomuriformis Using MALDI-TOF MS.

The present study compared two chemical-based methods, namely, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, to understand the misidentification of Exophiala dermatitidis and Exophiala phaeomuriformis. The study utilized 44 E. dermatitidis and 26 E. phaeomuriformis strains, which were partially treated with strong acids and bases for further evaluation. MALDI-TOF MS and ATR-FTIR spectroscopy data of the two Exophiala species were compared. Data groupings were observed for the chromic acid- and nitric acid-treated species when the black yeast sources were categorized as creosoted-oak sleepers, concrete sleepers, or dishwasher isolates. The MALDI-TOF MS data for the metalloenzyme-containing regions were consistent with the ATR-FTIR spectroscopy data. These results indicated that environmental isolates might contain metals not found in human isolates and might interfere with chemical-based identification methods. Therefore, MALDI-TOF MS reference libraries should be created for clinical strains and should exclude petroleum-associated environmental isolates.

[The effect of Tween-80 on the differentiation of Trichophyton mentagrophytes and Trichophyton rubrum strains with FT-IR spectroscopy]. / Trichophyton mentagrophytes ve Trichophyton rubrum kökenlerinin FT-IR spektroskopi ile ayriminda Tween-80 etkisi.

Trichophyton mentagrophytes and Trichophyton rubrum, are two of the frequently identified dermatophyte species in routine microbiology laboratories. Although newer technologies may assist in species-level identification, direct application of these methods usually require improvement in order to obtain reliable identification of these species. Earlier data have shown that dermatophytes may be identified with FT-IR spectroscopy although there are some limitations. In particular, the organic bond ranges in FT-IR spectra showed more irregularity because of the eucaryotic complexity of the molds. In this study, Tween-80 which is an inorganic molecule, was added to the dermatophyte growth medium in order to investigate its effect on FT-IR spectroscopy analysis of dermatophytes. Nine reference dermatophyte strains [5 T.mentagrophytes complex (T.asteroides CBS 424.63, T.erinacei CBS 344.79, CBS 511.73, CBS 677.86, T.mentagrophytes CBS 110.65) and 4 T.rubrum complex strains with different morphotypes (T.fluviomuniense CBS 592.68, T.kuryangei CBS 422.67, T.raubitschekii CBS 102856, T.rubrum CBS 392.58)] were included in the study. All strains were cultured on Sabouraud glucose agar either with or without 1% Tween-80 for three weeks. After the incubation period, superficial scrapings from each dermatophyte colony were analyzed using FT-IR spectroscopy. All measurements were performed in transmission mode between 4400 and 400 cm-1. Numerous spectral window data were analyzed by principal component analysis and hierarchical clustering was performed. The second derivations of spectral ranges revealed clear grouping of T.mentagrophytes complex and T.rubrum complex in association over five separate spectral ranges. The findings also showed that while all of the T.mentagrophytes strains contained lipid compounds in their mold structure after Tween-80 incubation (p< 0.025), T.rubrum strains did not. Based on these results, it was concluded that culture medium containing Tween-80 was sufficient to enable differentiation of T.mentagrophytes complex from T.rubrum complex by FT-IR spectroscopy. This effect might be attributed to the possible transfer of lipid compounds from culture to cell structure during growth. Further studies with the use of large number of reference strains and clinical isolates exposed to different environmental factors, such as antifungal agents and inorganic ions, are needed to support these data indicating favorable effect of Tween-80 on the differentiation of T.mentagrophytes and T.rubrum complexes by FT-IR spectroscopy.