Effects of emodin on the gene expression profiling of human breast carcinoma cells.
BACKGROUND
The mechanism of emodin-mediated cell apoptosis has been investigated extensively in many types of human cancer cells. Our previous study demonstrated that emodin induced apoptosis through the decrease of Bcl-2/Bax ratio and the increase of cytoplasm cytochrome c concentration in human breast cancer BCap-37 cells. However, emodin's reaction to breast cancer cells remains elusive.


METHODS
An apoptosis-associated cDNA microarray comprised of 458 known genes, namely, death receptors, calpains, death kinases, granzymes, DNA fragmentation proteins, caspases and Bcl-2 family, was used to determine the impact of emodin in breast cancer BCap-37 cells. Furthermore, the candidate emodin target genes were further evaluated via real-time quantitative PCR and Western blot analysis.


RESULTS
We found that gene expression profiling in human breast cancer BCap-37 cells was altered when exposed to emodin. Thirty of the unique genes that were either induced or repressed in response to emodin-induced apoptosis were also identified. A follow-up study characterized p53, emodin-induced gene, IGF-2, and emodin-repressed gene, and the downstream proteins were also seen as possible molecular targets of emodin.


CONCLUSIONS
Data from this study provide novel evidence that emodin induces gene expression profiling changes, but has no effects on caspases. In addition, the p53 pathway may cooperate with the IGF-2 pathway, resulting in an emodin-induced apoptosis through disruption of the mitochondrial signaling pathway in BCap-37 cells.
Huang
Zhiwei
Z
Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, PR China.
Chen
Guichen
G
Shi
Ping
P
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics*; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004642:Emodin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D053218:Receptors, Death Domain / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D047428:Protein Kinase Inhibitors; D053218:Receptors, Death Domain; D007335:Insulin-Like Growth Factor II; D053148:Caspase 3; D004642:Emodin