Synergistic apoptosis of MCF-7 breast cancer cells by 2-methoxyestradiol and bis(ethyl)norspermine Journal Article
| Authors: | Nair, S. K.; Verma, A.; Thomas, T. J.; Chou, T. C.; Gallo, M. A.; Shirahata, A.; Thomas, T. |
| Article Title: | Synergistic apoptosis of MCF-7 breast cancer cells by 2-methoxyestradiol and bis(ethyl)norspermine |
| Abstract: | 2-Methoxyestradiol (2ME) is an estradiol metabolite with anti-tumor and anti-angiogenic properties. We studied the effect of 2ME on apoptosis of MCF-7 breast cancer cells and explored a combination therapy using 2ME and a polyamine analogue, bis(ethyl)norspermine (BE-3-3-3). Determination of viable cells on day 4 of treatment with 2ME/BE-3-3-3 combinations showed synergistic effects by Chou-Talalay analysis. APO-BRDU analysis showed that there was only 1.5 ± 0.5% apoptosis at 200 nM 2ME and 3.7 ± 1.7% in the presence of 2.5 μM BE-3-3-3. Combination of 200 nM 2ME and 2.5 μM BE-3-3-3 resulted in 52.2 ± 2.6% apoptosis. Up to 90% of the cells underwent apoptosis in the presence of 1000 nM 2ME and 2.5 μM BE-3-3-3. Combination treatments resulted in total disruption of microtubules and depletion of putrescine, spermidine and spermine. In addition, phosphorylation of Akt and nuclear localization of cyclin D1 were altered by 2ME/BE-3-3-3 combination. Our results suggest an important strategy to induce apoptosis of breast cancer cells, with potential applications in therapy. © 2006 Elsevier Ireland Ltd. All rights reserved. |
| Keywords: | protein kinase b; controlled study; protein phosphorylation; human cell; drug potentiation; cell viability; cell cycle; apoptosis; microscopy, confocal; cancer cell culture; cell line, tumor; breast neoplasms; phosphorylation; drug synergism; blotting, western; proto-oncogene proteins c-akt; cell nucleus; cyclin d1; estradiol; microtubule; nuclear localization signal; 2 methoxyestradiol; broxuridine; bromodeoxyuridine; breast cancer cells; 2-methoxyestradiol; polyamine analogue; norspermine; putrescine; spermidine; spermine |
| Journal Title: | Cancer Letters |
| Volume: | 250 |
| Issue: | 2 |
| ISSN: | 0304-3835 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2007-06-08 |
| Start Page: | 311 |
| End Page: | 322 |
| Language: | English |
| DOI: | 10.1016/j.canlet.2006.10.027 |
| PUBMED: | 17184909 |
| PROVIDER: | scopus |
| PMCID: | PMC1899838 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 17 November 2011" - "CODEN: CALED" - "Source: Scopus" |
