Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FTY720 (fingolimod), a novel immunosuppressant, was found to become biologically activated by phosphorylation into FTY720-1-phosphate (FTY720-P), which is a high-affinity agonist for sphingosine-1-phosphate (sphingosine-1-P)-receptors. FTY720 has also been reported to have a strong antitumor activity. The association between the phosphorylation of FTY720 and the growth inhibition of FTY720 against cancer cells are still not completely understood. In this study, we investigated the effects of FTY720, sphingosine, and their related compounds on the proliferation of human breast cancer cell lines (MCF-7, MDA-MB-231 and Sk-Br-3) and human colon cancer cell lines (HCT-116 and SW620). Non-phosphorylated FTY720, sphingosine and an FTY720 derivative, ISP-I-55, showed significant growth inhibition against these cells, with IC50 values of 5-20 microM at 48 h post-drug treatment. We confirmed that FTY720 induces the activation of a major mitogen-activated protein kinase, JNK, without the activation of p38 and down-regulation of phospho-ERK in MCF-7 breast cancer cells. In contrast, the phosphorylated derivatives, FTY720-P and sphingosine-1-P, as well as a phosphinane FTY720 derivative, cFTY720-P, did not inhibit the growth of the cells in the concentration range of 5-50 microM, whereas FTY720-P and sphingosine-1-P slightly induced the growth of MCF-7 cells. Combining FTY720 with dimethylsphingosine, a sphingosine kinase inhibitor, augmented the inhibitory effect of FTY720. These results indicate that the antiproliferative activity of FTY720 does not result from its phosphorylation, either endogenous or exogenous.
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PMID:Effects of phosphorylation of immunomodulatory agent FTY720 (fingolimod) on antiproliferative activity against breast and colon cancer cells. 1852 51

Studies suggest consuming soy may protect women from breast cancer. In this study, lifetime exposure to 20%, 5% and 1% ISP in MTB-IGFIR mice (mammary-specific expression of IGF-IR) were evaluated to determine whether ISP could protect against mammary tumorigenesis. MTB-IGFIR mice fed ISP diets displayed increased mammary tumor incidence and reduced tumor latency compared to mice fed 20% casein. To evaluate whether a diet containing a less refined form of soy could protect against mammary tumor development MTB-IGFIR mice were fed Teklad 2018 (contains soybean meal). MTB-IGFIR mice fed the Teklad 2018 diet were completely protected against mammary tumor development. To determine whether dietary ISP was sufficient to induce mammary tumorigenesis, MTB-IGFIR mice were fed Teklad 2018ISP (soybean meal of Teklad 2018 was replaced with an equivalent amount of ISP). Only two of 10 MTB-IGFIR mice fed Teklad 2018ISP developed mammary tumors. This study demonstrates the complex interaction between soy and other dietary components in modifying mammary tumor development.
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PMID:Isolated Soy Protein Promotes Mammary Tumor Development Induced by the Type I Insulin-like Growth Factor Receptor in Transgenic Mice. 3269 62