Ayyappan 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
- School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam – 690 525, Kerala, India
- 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.
Nitish Sathyanrayanan, Sandesh Ganji and Holenarsipur Gundurao Nagendra.
Insilico Analysis of hypothetical proteins from Leishmania donovani: A Case study of a membrane protein of the MFS class reveals their plausible roles in drug resistance
Kala-azar or visceral leishmaniais (VL), caused by protozoan parasite Leishmania donovani, is one of the leading causes of morbidity and mortality in Bihar, India (Guerin et al. 2002; Mubayi et al. 2010). The disease is transmitted to the humans mainly by the vector, Phlebotmus argentipes, commonly known as Sand fly. The majority of VL (> 90%) occurs in only six countries: Bangladesh, India, Nepal, Sudan, Ethiopia and Brazil (Chappuis et al. 2007). In the Indian subcontinent, about 200 million people are estimated to be at risk of developing VL and this region harbors an estimated 67% of the global VL disease burden. The Bihar state only has captured almost 50% cases out of total cases in Indian sub-continent (Bhunia et al. 2013). ‘Conserved hypothetical’ proteins pose a challenge not just to functional genomics, but also to biology in general (Galperin and Koonin 2004). Leishmania donovani (strain BPK282A1) genome consists of a staggering ∼65% of hypothetical proteins. These uncharacterized proteins may enable better appreciation of signalling pathways, general metabolism, stress response and even drug resistance.