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Comparative proteomic analysis reveals growth inhibition by 3-N-alkyloxyestradiol derivative (SERM) in prostate cancer cells.

ABSTRACT: In this study we evaluated the proteomic profile of PC-3 cells treated with novel, 3-N-alkyloxyestradiol derivative, 3-[2-diisopropylamino]-ethoxy-D1,3,5 (10)-estrien-17-one (DI) (USPTO #7,687,486).The growth inhibitory potential of DI was determined by the National Cancer Institute (NCI) Developmental Therapeutics Program. 2-D gel electrophoresis and mass spectrometry were employed to identify differentially expressed proteins after treatment with DI.Growth inhibitory (GI(50)) results showed that DI inhibited the growth of PC-3 and DU-145 cells, at 13.9 ?M and 30.8 ?M, respectively. Out of the proteins differentially expressed, five were selected for identification with four of those being successfully identified. The identified proteins play a role in protein folding, cell motility, carbohydrate biosynthesis, and carbohydrate degradation.Our studies resulted in the identification of targets associated with the glycolytic pathway and cell motility which have been implicated in the development and progression of many cancers.

SUBMITTER: Green JE

PROVIDER: S-EPMC4135547 | biostudies-literature | 2014 Jul-Aug

REPOSITORIES: biostudies-literature

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Comparative proteomic analysis reveals growth inhibition by 3-N-alkyloxyestradiol derivative (SERM) in prostate cancer cells.

Green Jennifer E JE Cooperwood John S JS Taka Equar E Soliman Karam Fa KF Goodman Carl B CB Reams Romonia Renee RR

Cancer genomics & proteomics 20140701 4

<h4>Background/aim</h4>In this study we evaluated the proteomic profile of PC-3 cells treated with novel, 3-N-alkyloxyestradiol derivative, 3-[2-diisopropylamino]-ethoxy-D1,3,5 (10)-estrien-17-one (DI) (USPTO #7,687,486).<h4>Materials and methods</h4>The growth inhibitory potential of DI was determined by the National Cancer Institute (NCI) Developmental Therapeutics Program. 2-D gel electrophoresis and mass spectrometry were employed to identify differentially expressed proteins after treatment ...[more]

PMID: 25048348

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Project description:BackgroundProstate cancer is a leading cause of cancer-related death in men worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) protein family that is expressed in the majority of human tumors including prostate cancer, but is barely detectable in terminally differentiated normal cells. Downregulation of survivin could sensitize prostate cancer cells to chemotherapeutic agents in vitro and in vivo. Selenium is an essential trace element. Several studies have shown that selenium compounds inhibit the growth of prostate cancer cells. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the underlying mechanisms.MethodsExpression of survivin was analyzed in a collection of normal and malignant prostatic tissues by immunohistochemical staining. In vitro studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The effect of selenium on survivin expression was analyzed by Western blotting and semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting cells with a short hairpin RNA (shRNA) designed against survivin. Cell proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)- 2,5-Diphenyltetrazolium Bromide (MTT) assay and apoptosis by propidium iodide staining followed by flow cytometry analysis. Finally, in vivo tumor growth assay was performed by establishing PC-3M xenograft in nude mice and monitoring tumor growth following transfection and treatment.ResultsWe found that survivin was undetectable in normal prostatic tissues but was highly expressed in prostate cancers. Survivin knockdown or selenium treatment inhibited the growth of prostate cancer cells, but the selenium effect was modest. In contrast to what have been observed in other cell lines, selenium treatment had little or no effect on survivin expression in several androgen-independent prostate cancer cell lines. Survivin knockdown sensitized these cells to selenium growth inhibition and apoptosis induction. In nude mice bearing PC-3M xenografts, survivin knockdown synergizes with selenium in inhibiting tumor growth.ConclusionsSelenium could inhibit the growth of hormone-refractory prostate cancer cells both in vitro and in vivo, but the effects were modest. The growth inhibition was not mediated by downregulating survivin expression. Survivin silencing greatly enhanced the growth inhibitory effects of selenium.

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Comparative proteomic analysis reveals growth inhibition by 3-N-alkyloxyestradiol derivative (SERM) in prostate cancer cells.

Publications

Comparative proteomic analysis reveals growth inhibition by 3-N-alkyloxyestradiol derivative (SERM) in prostate cancer cells.

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