Targeting 1alpha,25-dihydroxyvitamin D3 antiproliferative insensitivity in breast cancer cells by co-treatment with histone deacetylation inhibitors

The Journal of Steroid Biochemistry and Molecular Biology
Claire M BanwellMoray J Campbell

Abstract

Proliferation of the non-malignant breast epithelial cell line, MCF-12A, is sensitively and completely inhibited by 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) (ED90 = 70 nM), We used real time RT-PCR to demonstrate that the relative resistance to 1alpha,25(OH)(2)D(3) of MDA-MB-231 cells (ED50 > 100 nM) correlated with significantly reduced Vitamin D receptor (VDR) and increased NCoR1 nuclear receptor co-repressor mRNA (0.1-fold reduction in VDR and 1.7-fold increase in NCoR1 relative to MCF-12A (P < 0.05)). This molecular lesion can be targeted by co-treating cells with 1alpha,25(OH)(2)D(3) or potent analogs and the histone deacetylation inhibitor trichostatin A (TSA). For example, the co-treatment of 1,25-dihydroxy-16,23,Z-diene-26,27-hexafluoro-19-nor Vitamin D(3) (RO-26-2198) (100 nM) plus TSA results in strong additive antiproliferative effects in MDA-MB-231 cells. This may represent novel chemotherapeutic regime for hormone insensitive breast cancer.

References

Feb 1, 1992·International Journal of Cancer. Journal International Du Cancer·T M PaineP J Dawson
Aug 1, 1997·Molecular Carcinogenesis·C W MillerH P Koeffler
Jan 8, 1999·Biochemical and Biophysical Research Communications·T TagamiJ L Jameson
Jul 6, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·P PollyC Carlberg

❮ Previous
Next ❯

Citations

Sep 24, 2005·Cancer Chemotherapy and Pharmacology·Mark G AndersonJ Ruth Wu-Wong
Apr 17, 2008·The Proceedings of the Nutrition Society·James Thorne, Moray J Campbell
Feb 16, 2010·The Journal of Steroid Biochemistry and Molecular Biology·S EssaJ Reichrath
Nov 12, 2014·PloS One·Manuel CorreiaMaria Teresa Neves-Petersen
Feb 25, 2011·PloS One·V'yacheslav Lehen'kyiNatalia Prevarskaya
Sep 23, 2008·The International Journal of Biochemistry & Cell Biology·James L ThorneBryan M Turner
Jun 14, 2005·American Journal of Physiology. Renal Physiology·Adriana S DussoEduardo Slatopolsky
Mar 1, 2006·Expert Review of Endocrinology & Metabolism·Moray J Campbell, S Asad Abedin
Jun 5, 2014·International Journal of Cancer. Journal International Du Cancer·James L Thorne, Moray J Campbell
Apr 1, 2011·Clinical Epigenetics·Heidrun Karlic, Franz Varga
Aug 16, 2017·Clinical Epigenetics·Sebastiano BattagliaBarbara A Foster
Oct 19, 2019·International Journal of Molecular Sciences·Smriti Murali Krishna
Jan 27, 2006·World Journal of Gastroenterology : WJG·Oliver SchröderJürgen Stein
Apr 13, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Claire M BanwellMoray J Campbell
May 2, 2006·Molecular Cancer Therapeutics·Sonoko Masuda, Glenville Jones

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis