ERα signaling imparts chemotherapeutic selectivity to selenium nanoparticles in breast cancer
Abstract
The present study focuses on the synthesis of stable selenium nanoparticles (SeNPs) and the elucidation of their mechanism of action in preventing the growth of mammary tumors. Selenious acid and reduced glutathione in the presence of sodium alginate were used as precursors for synthesis of SeNPs. Cell viability and expression of apoptotic markers (pp38, Bax, and cytochrome c) were assessed in MCF-7 and MDA-MB-231 breast cancer cells treated with SeNPs. Reduction in tumor volume was measured in rats with dimethylbenz[a]anthracene-induced mammary tumors. Synthesized SeNPs ranged in size from 40 to 90 nm and were stable up to 3 months of storage. We report that SeNP-induced cell death and expression of pp38, Bax, and cytochrome c were significantly higher in estrogen receptor-α (ERα)–positive cells (MCF-7) but not in ERα-negative cells (MDA-MB-231). Interestingly, animals showing significant decrease in tumor volume (small tumors) had lower levels of ERα as compared with animals showing a nonsignificant decrease in tumor volume (large tumor). This is the first report in our knowledge suggesting that the anticancer activity of SeNPs correlates with the level of ERα in breast cancer cells both in vivo and in vitro.
Graphical Abstract
MCF-7 cells, which are rich in ERα receptors are more susceptible to apoptosis when treated with SeNPs as compared with SeNPs–treated MDA-MB-231 cells, which do not have many ERα receptors. Thus, we propose a causal relationship between the levels of ERα and SeNPs–mediated cell death.
Key words: Selenium nanoparticles, ERα, Apoptosis, DMBA, Anticancer activity
To access this article, please choose from the options below
This research was supported by the Department of Science and Technology and the National National Institute of Pharmaceutical Education and Research.
PII: S1549-9634(11)00598-3
doi:10.1016/j.nano.2011.12.003
© 2011 Elsevier Inc. All rights reserved.
