In vitro model of normal, immortalized ovarian surface epithelial and ovarian cancer cells for chemoprevention of ovarian cancer

作者: Molly Brewer , J. Taylor Wharton , Jian Wang , Amanda McWatters , Nelly Auersperg

DOI: 10.1016/J.YGYNO.2005.01.051

关键词:

摘要: Abstract Background. Epithelial ovarian cancer has the highest mortality rate among gynecologic cancers. The synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), been used in chemoprevention of cancer. However, effectiveness its application for different populations questioned because genetic differences normal, high risk, and women with Objective. To explore similarities 4-HPR effects on epithelial cells which mimic women, normal surface epithelium to represent population immortalized premalignant changes, derived from malignant changes were as vitro models. Methods. Normal cells, incubated intervals increasing concentrations 4-HPR. Growth inhibition, fraction apoptotic expression apoptosis-related genes, including p53, p16, p21, caspase-3, mitochondrial permeability transition measured before after treatment. Results. Treatment produced growth inhibition apoptosis a dose-dependent manner all 3 cell types. strongest activation p53 pathway (NOE) while it caused largest increase MPT suggesting mechanism and/or these lines. 4-HPR, at concentration 10 μM, had maximal effect caspase-3 activity 72 h 48 although modest. Conclusions. showed differential response Although same endpoints induction present may be regulated through pathways. Implications. Clinical trials higher should prove beneficial.

参考文章(49)
Reuben Lotan, Cellular Biology of the Retinoids Springer, Berlin, Heidelberg. pp. 27- 42 ,(1995) , 10.1007/978-3-642-79706-4_3
D. Grillot, G. Nuñez, A. Benito, J. L. Fernández-Luna, Regulation and function of Bcl-2 during differentiation-induced cell death in HL-60 promyelocytic cells. American Journal of Pathology. ,vol. 146, pp. 481- 490 ,(1995)
Waun Ki Hong, Reuben Lotan, Retinoids in oncology Marcel Dekker. ,(1993)
Reuben Lotan, Ping Yue, Shi-Yong Sun, Waun K. Hong, Scott M. Lippman, Wanbo Li, Mediation of N-(4-hydoxyphenyl)retinamide-induced apoptosis in human cancer cells by different mechanisms. Cancer Research. ,vol. 59, pp. 2493- 2498 ,(1999)
Nobuhiko Oridate, Reuben Lotan, David F. Dohi, Garrett L. Walsh, Waun Ki Hong, Xiao Chun Xu, Jonathan C. Nesbitt, Jonathan M. Kurie, Chang Ping Zou, Yeul Hong Kim, Gil Ro Han, Retinoid Refractoriness Occurs during Lung Carcinogenesis Despite Functional Retinoid Receptors Cancer Research. ,vol. 55, pp. 5603- 5610 ,(1995)
Reuben Lotan, Waun Ki Hong, Chang Chun Zou, Jonathan M. Kurie, Dafna Lotan, Chang Ping Zou, Higher potency of N-(4-hydroxyphenyl)retinamide than all-trans-retinoic acid in induction of apoptosis in non-small cell lung cancer cell lines. Clinical Cancer Research. ,vol. 4, pp. 1345- 1355 ,(1998)
Andrew Berchuck, Al Elbendary, Laura Havrilesky, Gustavo C. Rodriguez, Robert C. Bast, Pathogenesis of ovarian cancers. Journal of The Society for Gynecologic Investigation. ,vol. 1, pp. 181- 190 ,(1994) , 10.1177/107155769400100302
Kornelia Polyak, Yong Xia, Jay L. Zweier, Kenneth W. Kinzler, Bert Vogelstein, A model for p53-induced apoptosis Nature. ,vol. 389, pp. 300- 305 ,(1997) , 10.1038/38525
Christina Thaller, Moshe Shalev, Anna Frolov, Gregor Eichele, Timothy C. Thompson, Russel H. Williams, Ozdal Dillioglugil, Dov Kadmon, Fenretinide Therapy in Prostate Cancer: Effects on Tissue and Serum Retinoid Concentration Journal of Clinical Oncology. ,vol. 18, pp. 3804- 3808 ,(2000) , 10.1200/JCO.2000.18.22.3804
Pierre Formstecher, Guido Kroemer, Santos A. Susin, Claude Méreau-Richard, Philippe Marchetti, Bertrand Joseph, Susanna Schraen-Maschke, Didier Métivier, Paola Costantini, Naoufal Zamzami, The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid can trigger apoptosis through a mitochondrial pathway independent of the nucleus. Cancer Research. ,vol. 59, pp. 6257- 6266 ,(1999)