Abstract | PURPOSE: EXPERIMENTAL DESIGN: MCF-7 cells stably expressing STS cDNA (MCF-7STS) were generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of estradiol sulfate (E2S) and bearing both MCF-7STS and wild-type MCF-7 (MCF-7WT) tumors were orally treated with STX64 and STX213. Treatment was given for 49 days followed by a recovery period of 35 days in which animals received only E2S. Mice were weighed, and tumor measurements were taken weekly. RESULTS: STX64 and STX213 exhibited potent STS inhibition in vivo. However, STX213 showed a greater duration of activity. In vehicle-treated nude mice receiving E2S, tumor volumes increased 5.5-fold for MCF-7WT and 3.8-fold for MCF-7STS after 49 days compared with day 0. MCF-7WT tumor growth was reduced by 56% by STX213 over the dosing period, and subsequent growth was retarded during the recovery period. All treatments fully inhibited growth of MCF-7STS tumors, and recovery of these tumors was significantly retarded (P<0.01). All compounds completely inhibited liver and tumor STS activity. Additionally, STS mRNA expression in the MCF-7STS tumors directly correlated with the corresponding STS enzyme activity. CONCLUSIONS: This study indicates that STS inhibitors attenuate hormone-dependent human breast cancer growth and therefore offer a potentially novel treatment for this condition.
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Authors | Paul A Foster, Simon P Newman, Surinder K Chander, Chloe Stengel, Roma Jhalli, Lawrence L W Woo, Barry V L Potter, Michael J Reed, Atul Purohit |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 12
Issue 18
Pg. 5543-9
(Sep 15 2006)
ISSN: 1078-0432 [Print] United States |
PMID | 17000691
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Azasteroids
- Enzyme Inhibitors
- RNA, Messenger
- STX 213
- Estradiol
- Steryl-Sulfatase
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Topics |
- Animals
- Azasteroids
(therapeutic use)
- Breast Neoplasms
(drug therapy, enzymology)
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Estradiol
(blood)
- Female
- Humans
- Liver
(drug effects, enzymology)
- Mice
- Mice, Nude
- Models, Biological
- Neoplasms, Hormone-Dependent
(drug therapy)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Steryl-Sulfatase
(antagonists & inhibitors, metabolism)
- Tissue Distribution
- Treatment Outcome
- Xenograft Model Antitumor Assays
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