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Doxazosin‐derived DZ‐3 Compound Enhances Apoptotic Ability of Maspin‐sensitized Prostate Cancer Cells
Author(s) -
Rybak Brynn,
Kyprianou Natasha
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a247
Subject(s) - maspin , doxazosin , prostate cancer , apoptosis , cancer research , cancer cell , cancer , cell culture , viability assay , chemistry , mtt assay , cell growth , metastasis , medicine , biology , biochemistry , blood pressure , genetics
The quinazoline‐based α1‐adrenoceptor antagonist, doxazosin, has previously been shown to induce apoptosis in both benign and malignant prostate cancer cells via the death receptor‐mediated pathway. Pharmacologic exploitation of doxazosin structure led the development of a series novel potential antitumor agents for prostate cancer treatment. In this study, we investigate the effect of a newly‐derived quinazoline‐based compound DZ‐3, on human prostate caner cell growth using the maspin‐overexpressing clone of human prostate cancer cells DU‐145 as a model. Maspin, a mammary serine protease inhibitor, has both tumor suppressive and antiangiogenic activity targeting tumor cell motility, invasion, and metastasis. Using the methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay, we determined cell viability in DU‐145 parental and DU‐145 maspin cells after treatment with DZ‐3. Exposure to DZ‐3 results in apoptotic cell death in both cell lines, however maspin expressing cells exhibited an enhanced sensitivity to DZ‐3‐induced apoptosis. Time course analysis of DZ‐3 treatment was subsequently performed different time in both cell lines and Western blotting was conducted to determine caspase activation. The results revealed that Maspin overexpression in prostate cancer cells resulted in an enhanced temporal activation in caspase‐8 vs the parental DU‐145 control cells. This study provides initial evidence on the ability the novel doxazosin‐derived DZ‐3 to induce caspase‐8mediated apoptosis in human prostate cancer cells.