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Indole-3-carbinol-induced death in cancer cells involves EGFR downregulation and is exacerbated in a 3D environment
| Content Provider | Semantic Scholar |
|---|---|
| Author | Moiseeva, Elena P. Fox, Louise H. Howells, Lynne M. Temple, Ludovic Manson, Margaret M. |
| Copyright Year | 2006 |
| Abstract | Indole-3-carbinol (I3C) is a promising anticancer dietary compound, which inhibits breast cancer in animal models. The objective of the current study was to characterize I3C-induced cell death in a panel of human breast tumorigenic cells (MCF7, MDA-MB-468, MDA-MB-231 and HBL100) in comparison with normal fibroblasts. Since epithelial cells are protected from cell death by a three-dimensional environment, 3D cell culture (collagen I gel and spheroids) was employed to investigate susceptibility to I3C. Cell viability in the presence of 256 μM I3C, a concentration close to the physiologically achievable range, was in the order fibroblasts = HBL100>MDA-MB-231>MCF7>MDA-MB-468 in monolayer culture. However, 3D culture conditions increased the susceptibility of MCF7 and MDA-MB-468 cancer cells towards I3C. I3C induced cell death in breast cancer MCF7, MDA-MB-468 and MDA-MB–231 cells via the mitochondrial apoptotic pathway. I3C significantly reduced levels of epidermal growth factor receptor (EGFR) in MDA-MB-468 after 6 h and in MDA-MB-231 and HBL100 cells after 30 h. Downregulation of EGFR in MDA-MB468 and MDA-MB-231 cells using an EGFR inhibitor resulted in apoptosis. EGFR modulation using EGF or an EGFR inhibitor markedly influenced viability and response to I3C in MDA-MB-468 cells in 3D conditions. EGFR expression was modulated by 3D conditions. Therefore, I3C-induced EGFR reduction in these cells is likely to be responsible for I3C-induced apoptosis. |
| Starting Page | 799 |
| Ending Page | 812 |
| Page Count | 14 |
| File Format | PDF HTM / HTML |
| DOI | 10.1007/s10495-006-5877-5 |
| PubMed reference number | 16532375 |
| Journal | Medline |
| Volume Number | 11 |
| Alternate Webpage(s) | https://lra.le.ac.uk/bitstream/2381/3436/1/Apoptosis%20final%202006.pdf |
| Alternate Webpage(s) | https://doi.org/10.1007/s10495-006-5877-5 |
| Journal | Apoptosis |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
