Fwd: Antiproliferative Activity of Derivatives of Ouabain, Digoxin and Proscillaridin A in Human MCF-7 and MDA-MB-231 Breast Cancer Cells.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Antiproliferative Activity of Derivatives of Ouabain, Digoxin and Proscillaridin A in Human MCF-7 and MDA-MB-231 Breast Cancer Cells.
To: mesothelioma77@gmail.com


[1]Biol Pharm Bull. 2008 Jun; 31(6): 1131-40
Winnicka K, Bielawski K, Bielawska A, Surazyński A

Three derivatives of ouabain, digoxin and proscillaridin A containing the carboxylic group instead of the lactone moiety were synthesized and examined for cytotoxicity in human breast cancer cells. Evaluation of the cytotoxicity of these compounds employing an MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MCF-7 and MDA-MB-231 breast cancer cells demonstrated that compound 3, the most active of the series, proved to be only slightly less potent than proscillaridin A. We evaluated the effects of these compounds 1-3 on change in intracellular Ca(2+), appearance of apoptosis, inhibition of DNA topoisomerase I and II, and the activity of caspase-3 in breast cancer cells. These studies indicate that the increase in potency for 3 may be related, in part, to an activation of caspase-3, increasing free calcium concentration and topoisomerase II inhibition. All these data emphasize the potential usefulness of these derivatives of cardiac glycosides as anticancer agents.



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Source: http://www.hubmed.org/display.cgi?uids=18520043
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Fwd: Effects of Phosphorylation of Immunomodulatory Agent FTY720 (Fingolimod) on Antiproliferative Activity against Breast and Colon Cancer Cells.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Effects of Phosphorylation of Immunomodulatory Agent FTY720 (Fingolimod) on Antiproliferative Activity against Breast and Colon Cancer Cells.
To: mesothelioma77@gmail.com


[1]Biol Pharm Bull. 2008 Jun; 31(6): 1177-81
Nagaoka Y, Otsuki K, Fujita T, Uesato S

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 IC(50) values of 5-20 muM 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 muM, 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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Source: http://www.hubmed.org/display.cgi?uids=18520051
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