Cytotoxic Effect of Disulfiram/Copper On Human Cervical Cancer Cell Lines and LGR5-Positive Cancer Stem-Like Cells

Background: Tumor resistance is a global challenge for tumor treatment. Cancer stem cells (CSCs) are the main population of tumor cells for drug resistance. We have reported that high aldehyde dehydrogenase (ALDH) activity represents a functional marker for cervical CSCs. Here we aim at disulfiram (DS), an ALDH inhibitor, that has the potential as a novel treatment to be used for cervical cancer.Methods: MTT assay, western blot, FCS analysis and sorting, vector construction and transfection, in vivo anti-tumor assays were performed using cervical cancer cell lines SiHa and HeLa. Cell cycle distribution and cell apoptosis were carried out by flow cytometry. The cytotoxicity of DS was detected by MTT assay and a xenograft cervical cancer model. Results: Disulfiram was cytotoxic to cervical cancer cell lines in a copper (Cu)-dependent manner. Disulfiram/copper (DS/Cu) complex induced deregulation of S-phase and inhibited the expression of stemness marker in cervical cancer cells. DS/Cu caused the death of LGR5-positive cervical cancer cells, a cancer stem-like cell population, which lead to cisplatin resistance in cervical cancer cells. Furthermore, DS/Cu complex had the greater antitumor efficacy on cervical cancer than cisplatin group in vitro and in vivo. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu complex may be superior to cisplatin because of targeting LGR5-positive cervical cancer stem-like cells in cervical cancer. Thus, the DS/Cu complex may represent a potential therapeutic strategy for cervical cancer patients.

Selective Leaching of Molybdenum from Bulk Concentrate by Electro-Oxidation

This paper proposes selective leaching of molybdenum from Mo/Cu complex bulk concentrates in a 5 M NaCl solution using the electro-oxidation method. Here, the effects of several factors such as pH, pulp density, current density, and temperatures were investigated. A higher leaching yield of Mo increased with increasing pH from 5 to 9 and decreased with increasing pulp density from 1 to 10%. A rise in current density did not help enhance Mo, and the elevating temperature did not always result in a higher leaching yield. Application of ultrasonic led to higher leaching yield of Mo. Ninety-two percent of leaching yield was obtained upon leaching of Mo in 5 M NaCl at 25 °C, pulp density of 5%, and the current density of 0.292 A/g under ultrasonic irradiation with a power of 27 kW. The resultant residue mainly consisted of chalcopyrite.

Role of catalytic nitrile decomposition in tricopper complex mediated direct partial oxidation of methane to methanol

Synthetic homogeneous system known to date performing methane to methanol conversion using O2 as terminal oxidant is unique and based on copper complex with piperazine-based ligand (Cu3L in Fig. 1) in a medium of acetonitrile. Prior work have shown that in order to achieve catalytic turnover, hydrogen peroxide is needed to regenerate the active site. We show in this paper that reaction solvent based on organic nitrile decompose concurrently with methane activation and that in the absence of either acetonitrile, Cu complex or hydrogen peroxide, the catalytic turnover does not happen. We show in this manuscript that the direct methane oxidation to methanol might have been mediated by catalytic Radziszewski oxidation between acetonitrile and H2O2. Additionally we have discovered that in the absence of methane, peroxide mediated acetonitrile decomposition also makes methanol via a background reaction which was hitherto unknown.

Novel nanoformulation of disulfiram with bacterially synthesized copper oxide nanoparticles for augmenting anticancer activity: an in vitro study

Background Disulfiram (DS), in the presence of copper (Cu), exhibited potent broad anticancer activity. However, its clinical application is limited due to the poor solubility and stability. Hence, a novel nanocombination of DS with bacterially synthesized copper oxide nanoparticles (CuO NPs) was prepared herein to improve the anticancer efficacy of the typical DS–Cu complex. Our design utilized the nanocharacterization and prooxidant effect-mediated anticancer activity of CuO NPs which may lead to enhanced cellular uptake and thus improved anticancer efficacy of this unique nanocomplex. Results The characterized DS–CuO NPs exhibited high stability in serum and the strongest selective anticancer activity, with the lowest half-maximum inhibitory concentration (IC50 < 15 nM), against human breast, lung and liver cancer cells, by >10-fold, compared to DS–Cu, CuO NPs and Cu. Importantly, DS–CuO NPs revealed better synergistic anticancer effect and higher cellular uptake than DS–Cu. Moreover, this novel nanocomplex showed higher prooxidant effect-mediated apoptosis and anti-metastatic potential. This was accomplished by elevating cellular reactive species content with inhibiting the antioxidant defenders (functional marker of cancer stem cells (aldehyde dehydrogenase) and nuclear factor erythroid 2-related factor2), matrix metallopeptidase 9 and NF-κB as well as enhancing p53 expression. Conclusion All of the aforementioned findings verified that this novel nanocomplex was capable of improving the therapeutic index of the conventional DS–Cu complex. The potent selective anticancer activity of this promising nanomedicine merits further investigation, as a separate future study, using animal models as preliminary step before its clinical application. Graphic abstract

Time-Resolved UV-IR Experiments that Suggest Photoactivated Fe-Cu Dinuclear Catalyst

This work reports the synthesis of a triethylsilyl-substituted Fe-Cu complex that provided cyclohexane solubility to conduct time-resolved UV-IR studies. These studies suggest that UV light induces a photochemically active heterodinuclear species for arene borylation catalysis.<br>