Aug
12
Mon
2013
Invited Talk: Screening flavonoids for NF-kB inhibitory effect as potential breast cancer therapy @ Sathyam Hall
Aug 12 @ 11:00 am – 11:20 am

ayyappanAyyappan Nair, Ph.D.
Head, Business Development (Technologies, Discovery Biology), Anthem Biosciences & DavosPharma, New Jersey, USA


Inhibition of NF-κB regulated gene expression by chrysoeriol suppresses tumorigenesis in breast cancer cells

Amrutha K1, Pandurangan Nanjan1, Sanu K Shaji1, Damu Sunilkumar1, Subhalakshmi K1, Rashmi U Nair1, Lakshmi Rajakrishna2, Asoke Banerji1, Ayyappan Ramesh Nair1*,2

  1. School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam – 690 525, Kerala, India
  2. Anthem Biosciences, No 49, Canara Bank Road, Bommasandra Industrial Area, Phase 1,  Hosur Road, Bangalore – 560 099, Karnataka, India

Abstract:  A large number of effective cancer-preventing compounds inhibit the activation of nuclear factor-κ B (NF-κB).  It has been previously demonstrated that some flavonoids that are a vital component of our diet inhibits this pathway. As a consequence, many flavonoids inhibit genes involved in various aspects of tumorigenesis and have thus emerged as potential chemopreventive candidates for cancer treatment. We studied the effect of 17 different flavonoids, including the highly evaluated quercetin on the NF-κB pathway, and on the expression of MMP-9 and COX-2 (two NF-κB regulated genes involved in metastasis) in the highly invasive human breast cancer cell line MDA-MB-231.  The findings suggest that not all the quercetin like flavone backbone compounds inhibit the NF-κB pathway, and that the highly hydoxylated flavonols quercetagetin and gossypetin did not inhibit this pathway, nor did it inhibit the expression of MMP-9 and COX-2.  This indicates a correlation between inhibition of NF-κB and subsequent suppression of these NF-κB regulated genes. Here, we also report the novel observation that the not so well characterized methoxylated flavone chrysoeriol inhibited the NF-κB pathway, and was most potent in reducing the expression of MMP-9 and COX-2.  Based on these observations, the cellular effects of chrysoeriol were evaluated in MDA-MB-231.  Chrysoeriol caused cell cycle arrest at G2/M, inhibited migration and invasion, and caused cell death of macrophages that contributed to migration of these cancer cells.  These effects of chrysoeriol make it a potential therapeutic candidate for breast cancer metastasis.

Ayyappan

 

Aug
13
Tue
2013
Plenary Talk: Biosensor and Single Cell Manipulation using Nanopipettes @ Amriteshwari Hall
Aug 13 @ 10:06 am – 10:49 am

NaderNader Pourmand, Ph.D.
Director, UCSC Genome Technology Center,University of California, Santa Cruz


Biosensor and Single Cell Manipulation using Nanopipettes

Approaching sub-cellular biological problems from an engineering perspective begs for the incorporation of electronic readouts. With their high sensitivity and low invasiveness, nanotechnology-based tools hold great promise for biochemical sensing and single-cell manipulation. During my talk I will discuss the incorporation of electrical measurements into nanopipette technology and present results showing the rapid and reversible response of these subcellular sensors  to different analytes such as antigens, ions and carbohydrates. In addition, I will present the development of a single-cell manipulation platform that uses a nanopipette in a scanning ion-conductive microscopy technique. We use this newly developed technology to position the nanopipette with nanoscale precision, and to inject and/or aspirate a minute amount of material to and from individual cells or organelle without comprising cell viability. Furthermore, if time permits, I will show our strategy for a new, single-cell DNA/ RNA sequencing technology that will potentially use nanopipette technology to analyze the minute amount of aspirated cellular material.

Invited Talk: “Inside-out” NF-kappa B signaling in cancer and other pathologies @ Acharya Hall
Aug 13 @ 11:25 am – 11:40 am

ShigekiShigeki Miyamoto, Ph.D.
Professor, McArdle Laboratory for Cancer Research – UW Carbone Cancer Center
Department of Oncology, School of Medicine and Public Health
University of Wisconsin-Madison


“Inside-out” NF-κB signaling in cancer and other pathologies

The NF-κB/Rel family of transcription factors contributes to critical cellular processes, including immune, inflammatory and cell survival responses. As such, NF-κB is implicated in immunity-related diseases, as well as multiple types of human malignancies. Indeed, genetic alterations in the NF-κB signaling pathway are frequently observed in multiple human malignancies. NF-κB is normally kept inactive in the cytoplasm by inhibitor proteins. Extracellular ligands can induce the release of NF-κB from the inhibitors to allow its migration into the nucleus to regulate a variety of target genes.  NF-κB activation is also induced in response to multiple stress conditions, including those induced by DNA-damaging anticancer agents. Although precise mechanisms are still unclear, research from our group has revealed a unique nuclear-to-cytoplasmic signaling pathway. In collaboration with bioengineers, clinicians and pharmaceutical industry, our lab has developed new methods to analyze primary cancer patient samples and identified several compounds with different mechanisms that mitigate this cell survival pathway.  Further contributions from other labs have also revealed additional mechanisms and molecular players in this “inside-out” signaling pathway and expanded its role in other physiological and pathological processes, including B cell development, premature aging and therapy resistance of certain cancers. Our own new findings, along with these recent developments in the field, will be highlighted.

Shigeki

Delegate Talk: Pt-Pd decorated TiO2 nanotube array for the non-enzymatic determination of glucose in neutral medium @ Amriteshwari Hall
Aug 13 @ 4:25 pm – 4:36 pm
Delegate Talk: Pt-Pd decorated TiO2 nanotube array for the non-enzymatic determination of glucose in neutral medium @ Amriteshwari Hall | Vallikavu | Kerala | India

John Stanley, Satheesh Babu, Ramacahandran T and Bipin Nair


Pt-Pd decorated TiO2 nanotube array for the non-enzymatic determination of glucose in neutral medium

Rapidly expanding diabetic population and the complications associated with elevated glycemic levels necessitates the need for a highly sensitive, selective and stable blood glucose measurement strategy. The high sensitivity and selectivity of enzymatic sensors together with viable manufacturing technologies such as screen-printing have made a great social and economic impact. However, the intrinsic nature of the enzymes leads to lack of stability and consequently reduces shelf life and imposes the need for stringent storage conditions. As a result much effort has been directed towards the development of ‘enzyme-free’ glucose sensors (Park et al. 2006). In this paper, a non-enzymatic amperometric sensor for selective and sensitive direct electrooxidation of glucose in neutral medium was fabricated based on Platinum-Palladium (Pt–Pd) nanoparticle decorated titanium dioxide (TiO2) nanotube arrays. Highly ordered TiO2 nanotube arrays were obtained using a single step anodization process (Grimes C A and Mor G K 2009) over which Pt–Pd nanoparticles where electrochemically deposited. Scanning Electron Microscopy (SEM) analysis revealed the diameter of the TiO2 nanotubes to be approximately 40 nm. Elemental analysis after electrochemical deposition confirms the presence of Pt–Pd. Electrochemical characterization of the sensor was carried out using cyclic voltammetry technique (−1.0 to +1.0V) in phosphate buffer saline (PBS) pH 7.4. All further glucose oxidation studies were performed in PBS (pH 7.4). The sensor exhibited good linear response towards glucose for a concentration range of 1 μM to 20mM with a linear regression coefficient of R = 0.998. The electrodes are found to be selective in the presence of other commonly interfering molecules such as ascorbic acid, uric acid, dopamine and acetamidophenol. Thus a nonenzymatic sensor with good selectivity and sensitivity towards glucose in neutral medium has been developed.