RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells.

作者: Koen Brusselmans , Ellen De Schrijver , Johannes V. Swinnen , Walter Heyns , Guido Verhoeven

DOI:

关键词:

摘要: Fatty acid synthase (FASE), a key enzyme in the biosynthesis of fatty acids, is markedly overexpressed many human epithelial cancers, rendering it an interesting target for antineoplastic therapy. Here, using potent and highly sequence-specific mechanism RNA interference (RNAi), we have silenced expression FASE lymph node carcinoma prostate (LNCaP) cells. RNAi-mediated down-regulation resulted major decrease synthesis triglycerides phospholipids induced marked morphological changes, including reduction cell volume, loss cell-cell contacts, formation spider-like extrusions. Furthermore, silencing gene by RNAi significantly inhibited LNCaP growth ultimately induction apoptosis. Importantly striking contrast with cells, inhibition did not influence rate or viability nonmalignant cultured skin fibroblasts. These data indicate that opens new avenues toward study role overexpression tumor cells provides selective alternative to chemical inhibitors development

参考文章(39)
Sayda M. Elbashir, Jens Harborth, Winfried Lendeckel, Abdullah Yalcin, Klaus Weber, Thomas Tuschl, Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells Nature. ,vol. 411, pp. 494- 498 ,(2001) , 10.1038/35078107
Francis P. Kuhajda, Ellen S. Pizer, Nancy E. Davidson, Fawn D. Wood, Gary R. Pasternack, Christian Jackisch, Inhibition of Fatty Acid Synthesis Induces Programmed Cell Death in Human Breast Cancer Cells Cancer Research. ,vol. 56, pp. 2745- 2747 ,(1996)
Ellen S. Pizer, Ji-Nong Li, Michele K. Evans, Myriam Gorospe, Francis J. Chrest, Wan Fang Han, Tirukalikundram S. Kumaravel, Pharmacological Inhibition of Fatty Acid Synthase Activity Produces Both Cytostatic and Cytotoxic Effects Modulated by p53 Cancer Research. ,vol. 61, pp. 1493- 1499 ,(2001)
Francis P. Kuhajda, Ellen S. Pizer, Henry S. Heine, Fawn D. Wood, Gary R. Pasternack, Fedor E. Romantsev, Inhibition of Fatty Acid Synthesis Delays Disease Progression in a Xenograft Model of Ovarian Cancer Cancer Research. ,vol. 56, pp. 1189- 1193 ,(1996)
Binqiu Liu, Yingqiang Wang, Kerry Fillgrove, Vernon Anderson, Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells Cancer Chemotherapy and Pharmacology. ,vol. 49, pp. 187- 193 ,(2002) , 10.1007/S00280-001-0399-X
Yu-An Yang, Wan Fang Han, Patrice J Morin, Francis J Chrest, Ellen S Pizer, Activation of Fatty Acid Synthesis during Neoplastic Transformation: Role of Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Experimental Cell Research. ,vol. 279, pp. 80- 90 ,(2002) , 10.1006/EXCR.2002.5600
Jagan N. Thupari, Michael L. Pinn, Francis P. Kuhajda, Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity. Biochemical and Biophysical Research Communications. ,vol. 285, pp. 217- 223 ,(2001) , 10.1006/BBRC.2001.5146
Chandrika J Piyathilake, Andra R Frost, Upender Manne, Walter C Bell, Heidi Weiss, Douglas C Heimburger, William E Grizzle, None, The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung Human Pathology. ,vol. 31, pp. 1068- 1073 ,(2000) , 10.1053/HUPA.2000.9842
Karin Moelling, Thomas Schulze, Marie-Therés Knoop, John Kay, Raymond Jupp, George Nicolaou, Laurence H. Pearl, In vitro inhibition of HIV-1 proteinase by cerulenin FEBS Letters. ,vol. 261, pp. 373- 377 ,(1990) , 10.1016/0014-5793(90)80595-A