Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer

Formic acid electro-synthesis from carbon dioxide in a room temperature ionic liquid.

The novel synthesis of formic acid has been achieved in a room temperature ionic liquid via the reaction of electro-activated carbon dioxide and protons on pre-anodised platinum. Only mild reaction conditions of room temperature and 1 atm CO(2) were used. This work highlights the effect of pre-anodisation on Pt surfaces

A comparison of the cyclic voltammetry of the Sn/Sn(II) couple in the room temperature ionic liquids N-butyl-N-methylpyrrolidinium dicyanamide and N-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide: solvent induced changes of electrode reaction mechanism.

The Sn/Sn(II) couple is studied in the room temperature ionic liquids N-butyl-N-methylpyrrolidinium dicyanamide, [C(4)mpyrr][N(CN)(2)] and N-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, [C(4)mpyrr][NTf(2)] using cyclic voltammetry. The Sn(II) species is introduced into each of the ionic liquids by dissolving either SnCl(2) or Sn(CF(3)SO(3))(2). The diffusion coefficient of the Sn(II) species produced is found to vary with the ionic liquid, partly reflecting the difference in the viscosity of the two liquids, but also to vary with the Sn(II) salts used, indicating that different Sn(II) species may be present. The mechanism for the stripping of deposited tin is found to change with potential and also vary with the Sn(II) salt/ionic liquid combination used. In [C(4)mpyrr][N(CN)(2)] the mechanism for the tin stripping process is broadly similar for both of the Sn(II) salts used indicating that the morphology of the tin deposit is similar and that the stripping mechanism is largely independent of the Sn(II) salt anion. In [C(4)mpyrr][NTf(2)] a large difference was seen in the voltammetry of the different Sn(II) salts. Tafel analysis is used to show that the mechanism of the oxidation of Sn is sensitive to the solvent, the salt and the potential. The rate determining step was found to vary between the first electron transfer, the second electron transfer and a step likely involving reactions of a Sn(+) intermediate

Room temperature ionic liquid as solvent for in situ Pd/H formation: hydrogenation of carbon-carbon double bonds.

This work undertakes mechanistic studies of H(+) reduction on a palladium microelectrode in a room temperature ionic liquid. It was found that the electrode was initially in a partially passivated state in [NTf(2)](-) based RTILs and that pre-anodisation of the electrode surface has a dramatic effect on the reversibility of the system, also triggering a change from hydrogen evolution to hydrogen absorption. Theoretical modelling supported the idea of Pd/H formation under these conditions. Utilising Pd/H as an activated hydrogen source, a proof-of-concept method for hydrogenation of multiple bond containing organic molecules by in situ generation of Pd/H via reduction of H(+) on palladium in a room temperature ionic liquid has been demonstrated

Towards the electrochemical quantification of the strength of garlic.

A simple but sensitive technique has been demonstrated towards the electroanalytical quantification of the strength of garlic. This technique can also be used to quantify dialkyldisulfides. The cyclic voltammetry of bromide was found to be a sensitive electrochemical probe, electrogenerated bromine reacting with dialkyldisulfides to catalytically regenerate bromide, resulting in a significant increase in peak current. A linear response of current vs. concentration was observed between 0.1 and 15 mM dipropyldisulfide at edge plane pyrolytic graphite (EPPG) electrodes; a smaller range up to ca. 5 mM was available at screen printed carbon electrodes (SPCEs), with a detection limit (from 3σ) of 0.067 mM. The response of diallyldisulfide was found to be essentially identical. Shaking garlic puree in acetonitrile for 5 minutes, followed by dilution with water then recording the voltammetry at the cheap, disposable SPCE gave a linear trend in current with respect to the quantity of garlic present, corresponding to the diallyldisulfide extracted. This has potential applications in monitoring the garlic content of medicinal supplements, batch-to-batch variation and the stability of garlic during storage