Expression of retinoic acid receptor-beta sensitizes prostate cancer cells to growth inhibition mediated by combinations of retinoids and a 19-nor hexafluoride vitamin D3 analog

Endocrinology
M J CampbellH P Koeffler

Abstract

Retinoids and analogs of vitamin D3 may achieve greater in vivo applications if the toxic side effects encountered at pharmacologically active doses could be alleviated. These seco-steroid hormones often act in concert, and therefore, we attempted to dissect these interactions by isolating combinations of receptor-selective retinoids and a potent vitamin D3 analog [1alpha,25(OH)2-16ene-23-yne-26,27,F6-19nor-D3, code name LH] that were potent inhibitors of prostate cancer cell growth at low, physiologically safer doses. Using a panel of prostate cancer cell lines representing progressively more transformed phenotypes, we found that the LNCaP cell line (least transformed) was either additively or synergistically inhibited in its clonal growth by LH and various naturally occurring and receptor-selective retinoids, the most potent combination being with a retinoic acid receptor (RAR)betagamma-selective retinoid (SR11262). The effect was not found with either PC-3 (intermediate transformation) or DU-145 (most transformed). We also undertook RT-PCR to examine the subtypes of RARs present, and we found that PC-3 and DU-145 did not express RARbeta. Stable expression of RARbeta into the RARbeta-negative PC-3 cells resulted in increased ...Continue Reading

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Citations

Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·K M SommerK Swisshelm
Jun 11, 2008·Applied Microbiology and Biotechnology·Nallasamy KumaresanSukumaran Umesh-Kumar
Jan 11, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Mei-Chih ChenChuan-Mu Chen
Feb 6, 2008·Molecular and Cellular Neurosciences·James K J DissDavid S Latchman
Nov 18, 2005·Biochemical and Biophysical Research Communications·Yan-Ru LouPentti Tuohimaa
Mar 16, 2017·Molecular and Cellular Endocrinology·Moray J Campbell
Feb 11, 2003·Journal of Cellular Biochemistry·Sylvia ChristakosAngela Porta
May 21, 2016·Nuclear Receptor Research·Mark D Long, Moray J Campbell
Nov 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Zengli YuYong Li
Mar 1, 2006·Expert Review of Endocrinology & Metabolism·Moray J Campbell, S Asad Abedin
Jun 20, 2019·Cells·Masaki ShiotaMasatoshi Eto
Dec 7, 2019·Cancers·Orsola di Martino, John S Welch
Oct 31, 2017·Endocrinology and Metabolism Clinics of North America·Moray J Campbell, Donald L Trump
Jul 4, 2003·The Journal of Nutrition·Donna M PeehlDavid Feldman
Jul 26, 2008·The International Journal of Biochemistry & Cell Biology·Kun Cai, Lorraine J Gudas

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