PTEN inactivation induces epithelial-mesenchymal transition and metastasis by intranuclear translocation of β-catenin and snail/slug in non-small cell lung carcinoma cells

Perumal, Elumalai,So Youn, Kim,Sun, Shin,Seung-Hyun, Jung,Suji, Min,Jieying, Liu,Yeun-Jun, Chung Elsevier 2019 Lung cancer Vol.130 No.-

<P><B>Abstract</B></P> <P><B>Objective</B></P> <P>Epithelial-mesenchymal transition (EMT) is the key event in distant metastasis of diverse tumors including lung cancer. Recent evidence suggests the involvement of phosphatase and tensin homolog (PTEN) in EMT phenotypes. However, the molecular mechanism of EMT induced by PTEN inactivation is not clear in lung cancer. We aimed to investigate the role of PTEN inactivation in acquisition of EMT in lung cancer cells.</P> <P><B>Methods</B></P> <P>We knocked out the PTEN in PTEN proficient lung cancer cells lines (A549 and NCI-H460) using CRISPR/Cas-9 system and observed the growth, EMT phenotypes, and EMT related molecules. We also explored the in vivo effect of PTEN inactivation on tumor cell growth and distant metastasis using nude mouse injection.</P> <P><B>Results</B></P> <P>PTEN knockout (KO) cells showed faster growth, migration and invasion than PTEN wild-type (WT) cells. When we injected the cells into nude mice, PTEN-KO cells showed faster growth and higher metastatic potential. In PTEN-KO cells, the levels of phosphorylated AKT (Ser-473 and Thr-308) were profoundly elevated and the expressions of phosphorylated GSK-3β (Ser9, inactive form) increased, while that of β-catenin decreased. Regarding the EMT markers, the expression of E-cadherin decreased but those of N-cadherin, vimentin and MMP-2 increased in the PTEN-KO cells. Especially, PTEN-KO cells showed the almost complete intra-nuclear shift of β-catenin and no β-catenin signal was observed in the cell membrane. Accordingly, PTEN-KO cells exhibited morphological changes such as loss of cell-to-cell contact, pseudopodia and the round shape, which are the typical phenotypes of EMT. Snail and Slug were also dominantly accumulated in the nucleus after PTEN inactivation.</P> <P><B>Conclusion</B></P> <P>All these data consistently support that PTEN inactivation contributes to EMT by nuclear translocation of β-catenin and Snail/Slug in lung cancer cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Epithelial-mesenchymal transition (EMT) is behind tumor invasion and metastasis. </LI> <LI> We examined the role of PTEN inactivation in EMT in lung cancer cells. </LI> <LI> Inactivated PTEN affects EMT by nuclear translocation of β-catenin and Snail/Slug. </LI> <LI> PI3K/AKT/GSK-3β pathway was essential for inducing EMT in PTEN inactivated cells. </LI> </UL> </P>

Potentiometric flow sensor for in-situ determination of electrogenerated electron mediator in an paired electrolysis cell

( Perumal Silambarasan ),( G. Muthuraman ),문일식 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

Instead of off-line potentiometric titrations for electron mediator’s quantification, in-situ determination can be an accurate method. Here in, we have initiated to monitor the electrochemically prepared mediator [Co(I)(CN)₅]^4- by in-situ flow sensor cell coupled with paired electrolysis cell. First, cyclic voltammetry peak current for a standard redox couple Fe(II)/Fe(III) with different concentration ratios was used in the flow sensor cell to check the developed method. Then the Chemically prepared [Co(I)(CN)₅]^4- in presence of 10 M KOH at different concentrations were analyzed by UV-Visible and potentiometric titration method and compared. Finally, the chemically prepared different concentration of Co(I) do monitored using selected electrode under the inert atmosphere by flow sensor cell. The resulted calibration plot used to derive the concentration of [Co(I)(CN)₅]^4-.

Real time potentiometric macro flow sensor: An innovative tool to monitor electrogenerated electron mediator in high concentrated electrolyte during electrolysis and air pollutants removal

( PERUMAL SILAMBARASAN ),( G. MUTHURAMAN ),문일식 한국공업화학회 2018 한국공업화학회 연구논문 초록집 Vol.2018 No.1

Review on Molecular and Chemopreventive Potential of Nimbolide in Cancer

Perumal Elumalai,Jagadeesan Arunakaran 한국유전체학회 2014 Genomics & informatics Vol.12 No.4

Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, theexact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapybased on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, anon-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plantsoffer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem(Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various humandiseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. Theprevious studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancercells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticanceractivity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related tocancer progression.

Interaction of Zwitterionic and Ionic Monomers with Graphene Surfaces

Perumal, Suguna,Raji, Atchudan,Cheong, In Woo American Chemical Society 2018 Langmuir Vol.34 No.23

<P>Measurement of the interaction force between two materials provides important information on various properties, such as adsorption, binding, or compatibility for coatings, adhesion, and composites. The interaction forces of zwitterionic and ionic monomers with graphite platelets (G) and reduced graphene oxide (rGO) surfaces were systematically investigated by atomic force microscopy (AFM) in air and water. The monomers examined were 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate (MPC), [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBE), [2-(acryloyloxy)ethyl]trimethylammonium chloride (ATC), and 2-methyl-2-propene-1-sulfonic acid sodium (MSS). The AFM studies revealed that MSS and SBE monomers with sulfonate units have stronger interaction forces with G surface in air and that MPC and ATC monomers with quaternary ammonium units have higher interaction forces in water. In the case of rGO surface, the monomers with quaternary ammonium units showed stronger interactions regardless of the medium. These interactions could be rationalized by the interaction mechanism between the monomers with graphene surfaces, such as cation−π for MPC and ATC and anion−π for MSS and SBE. Overall, cation−π interactions were effective in water, whereas anion−π interactions are effective in air with G surface. The adhesion values of MPC, SBE, ATC, and MSS on rGO were lower than the values measured on G surface. Among the monomers, MPC showed the highest dispersibility for aqueous graphene dispersions. Further, the adsorption of MPC on G and rGO surfaces was verified by high-resolution transmission electron microscopy and X-ray diffraction patterns.</P> [FIG OMISSION]</BR>

Effect of bimetal coated membrane electrode divided Clarks cell for online air pollutant sensor: A study by electrochemical removal at electroscrubbing plant

( Perumal Silambarasan ),( G. Muthuraman ),문일식 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

In the present investigation, Ag and Ag-Ni or Ag-Co metal ions coated Nafioni324 membrane electrode divided cell was developed and compared in amperometric detection of air pollutants. Ag and Ag-Ni or Ag-Co were chemically coated on the Nafion324 membrane and used in filter press technique to make a cell with one side having 0.1 M KOH electrolyte and gas phase cathodic half-cell. Based on the cyclic voltammetry and linear sweep voltammetry analyses, the gas phase redox peak was fixed for detection of selected gas pollutants. Then sense a selected air pollutants by amperometric method at different suitable applied voltage. The current with different feed concentration were compared with in-situ FTIR gas analyzer concentration and derived calibration plot.

Highly flexible memristive devices based on MoS₂ quantum dots sandwiched between PMSSQ layers

Perumal Veeramalai, Chandrasekar,Li, Fushan,Guo, Tailiang,Kim, Tae Whan The Royal Society of Chemistry 2019 Dalton Transactions Vol.48 No.7

<P>This paper reports a facile, cost effective method that uses an aqueous hydrothermal process for synthesizing two-dimensional molybdenum disulphide (MoS2) monolayer quantum dots (QDs) and their potential applications in flexible memristive devices. High-resolution transmission electron microscopy and atomic force microscopy images confirmed that the diameters of the synthesized MoS2 QDs with irregular shapes were in the range between 3 and 6 nm; their thicknesses were confirmed to lie between 1.0 and 0.8 nm, a clear indication that a monolayer of MoS2 QDs had been synthesized. Photoluminescence (PL) and time-resolved PL spectra of the MoS2 QDs revealed a strong emission in the blue region with a slower decay constant. Memristive devices fabricated by incorporating MoS2 QDs between poly(methylsilsesquioxane) ultrathin layers, which had been deposited on poly(ethylene terephthalate), demonstrated a high ON-OFF current ratio of ∼10<SUP>4</SUP>, stable retention, and excellent endurance in the relaxed state; these devices were also demonstrated to function properly during bending and in a bent state. The flexible memristive devices demonstrated an OFF state with a very low current of 10<SUP>−6</SUP> A. These results clearly show that ultrathin two-dimensional QDs have promising applications in high-performance flexible memristive devices.</P>

Consideration of bulk concentration change in transient current of rotating disc electrode for E’ reaction (quasi- reversible): Theoretical simulation and experimental validation

( Perumal Silambarasan ),심왕근,( G. Muthuraman ),문일식 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1

In the rotating disc electrode transient current, the bulk concentration considered as constant due to the non-electrolyzed solution. But, change in bulk concentration occurred in many paired electrolysis process with electrolysis time that is used for many applications. In this work, the transient current and concentration change in the rotating disc electrode (RDE) system is explained by solving the convection and diffusion equation for a quasi- reversible electron transfer. The mathematical models are solved by applying orthogonal collocation method. This approach enables us the current response and concentration change with electrolysis time. Experimental results compared with the theoretically simulated data. A good correlation found between the current and the RDE system. The possible expression derived in the present work for bulk concentration change can be used for continuous electrolysis system.

High-concentration graphene dispersion stabilized by block copolymers in ethanol

Perumal, Suguna,Lee, Hyang Moo,Cheong, In Woo Elsevier 2017 JOURNAL OF COLLOID AND INTERFACE SCIENCE - Vol.497 No.-

<P><B>Abstract</B></P> <P>This article describes a comprehensive study for the preparation of graphene dispersions by liquid-phase exfoliation using amphiphilic diblock copolymers; poly(ethylene oxide)-<I>block</I>-poly(styrene) (PEO-<I>b</I>-PS), poly(ethylene oxide)-<I>block</I>-poly(4-vinylpyridine) (PEO-<I>b</I>-PVP), and poly(ethylene oxide)-<I>block</I>-poly(pyrenemethyl methacrylate) (PEO-<I>b</I>-PPy) with similar block lengths. Block copolymers were prepared from PEO using the Steglich coupling reaction followed by reversible addition-fragmentation chain transfer (RAFT) polymerization. Graphite platelets (G) and reduced graphene oxide (rGO) were used as graphene sources. The dispersion stability of graphene in ethanol was comparatively investigated by on-line turbidity, and the graphene concentration in the dispersions was determined gravimetrically. Our results revealed that the graphene dispersions with PEO-<I>b</I>-PVP were much more stable and included graphene with fewer defects than that with PEO-<I>b</I>-PS or PEO-<I>b</I>-PPy, as confirmed by turbidity and Raman analyses. Gravimetry confirmed that graphene concentrations up to 1.7 and 1.8mg/mL could be obtained from G and rGO dispersions, respectively, using PEO-<I>b</I>-PVP after one week. Distinctions in adhesion forces of PS, VP, PPy block units with graphene surface and the variation in solubility of the block copolymers in ethanol medium significantly affected the stability of the graphene dispersion.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Estimating the compressive strength of HPFRC containing metallic fibers using statistical methods and ANNs

Perumal, Ramadoss,Prabakaran, V. Techno-Press 2020 Advances in concrete construction Vol.10 No.6

The experimental and numerical works were carried out on high performance fiber reinforced concrete (HPFRC) with w/cm ratios ranging from 0.25 to 0.40, fiber volume fraction (Vf)=0-1.5% and 10% silica fume replacement. Improvements in compressive and flexural strengths obtained for HPFRC are moderate and significant, respectively, Empirical equations developed for the compressive strength and flexural strength of HPFRC as a function of fiber volume fraction. A relation between flexural strength and compressive strength of HPFRC with R=0.78 was developed. Due to the complex mix proportions and non-linear relationship between the mix proportions and properties, models with reliable predictive capabilities are not developed and also research on HPFRC was empirical. In this paper due to the inadequacy of present method, a back propagation-neural network (BP-NN) was employed to estimate the 28-day compressive strength of HPFRC mixes. BP-NN model was built to implement the highly non-linear relationship between the mix proportions and their properties. This paper describes the data sets collected, training of ANNs and comparison of the experimental results obtained for various mixtures. On statistical analyses of collected data, a multiple linear regression (MLR) model with R2=0.78 was developed for the prediction of compressive strength of HPFRC mixes, and average absolute error (AAE) obtained is 6.5%. On validation of the data sets by NNs, the error range was within 2% of the actual values. ANN model has given the significant degree of accuracy and reliability compared to the MLR model. ANN approach can be effectively used to estimate the 28-day compressive strength of fibrous concrete mixes and is practical.