Carcinogenesis Advance Access published online on January 6, 2006
Carcinogenesis, doi:10.1093/carcin/bgi328
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1 Penn State College of Medicine, 500 University Drive, Hershey, PA 17033
* To whom correspondence should be addressed. Clinical chemoprevention trials of lung cancer have been somewhat disappointing and the development of highly effective chemopreventive agents is urgently needed. We previously showed that the organoselenium 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a potent chemopreventive agent in numerous preclinical animal models including lung tumor model that employs carcinogens found in tobacco smoke. The goal of this study is to define molecular targets that will be highly promising in the design of future chemoprevention trials of non-small cell lung cancer (NSCLC), which is by far the most common type of lung cancer cases. In the present investigation we showed that p-XSC at several doses (2.5, 5, 10, 20 µM) including physiological levels (2.5-5.0 µM) of selenium is capable of inhibiting cell growth in a dose-dependent manner and inducing apoptosis in three NSCLC cells (NCI-H460, NCI-1299, and A549). To clarify the mechanism involved at the molecular level, we focused only on NCI-460 cells and examined the effects of p-XSC on markers that are known to be critical in the development of NSCLC. Using western blot analysis, we showed that p-XSC reduced the expression of COX-2 and PLA2; although p-XSC inhibited both Akt and p-Akt but its effect was not significant. Using cDNA microarray approach (3,800 genes per array) we found that p-XSC up-regulates 22 genes by
Received September 20, 2005
Revised October 30, 2005
Accepted December 20, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Molecular targets of the chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate in human non small cell lung cancer
Karam El-Bayoumy 1 *,
Arunangshu Das 1,
Bhagavathi Narayanan 2,
Narayanan Narayanan 2,
Emerich S. Fiala 2,
Dhimant Desai 1,
Chinthalapally V. Rao 3,
Shantu Amin 1,
and
Raghu Sinha 1
2 New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987
3 The University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104
Karam El-Bayoumy, E-mail: kelbayoumy{at}aol.com
Abstract 
2-fold while down-regulates 13 genes by 
0.5 fold; these altered genes include transcriptional factors, growth factors and those involved in xenobiotic metabolism as well as pro- and anti-apoptotic genes. Expression of selected genes was confirmed by RT-PCR; p-XSC reduced the levels of COX-2, PLA2, NF
B and Cyclin D1 but enhanced the levels of GPX5. Collectively the results of this study showed that p-XSC alters several molecular markers in a manner that can account for its inhibitory effect of cell growth and induction of apoptosis; therefore p-XSC may be considered a promising candidate for clinical chemoprevention of NSCLC.
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