Histone Deacetylase Inhibitor SAHA Is a Promising Treatment of Cushing Disease

The Journal of Clinical Endocrinology and Metabolism
Jie LuPrashant Chittiboina

Abstract

Remission failure following transsphenoidal surgery in Cushing disease (CD) from pituitary corticotroph tumors (CtTs) remains clinically challenging. Histone deacetylase inhibitors (HDACis) are antitumor drugs approved for clinical use, with the potential to affect adrenocorticotropin hormone (ACTH) hypersecretion by inhibiting pro-opiomelanocortin (POMC) transcription. Testing the efficacy of suberoylanilide hydroxamic acid (SAHA) on human and murine ACTH-secreting tumor (AtT-20) cells. Cell viability, ACTH secretion (enzyme-linked immunosorbent assay), apoptosis, and gene expression profile were investigated on AtT-20 cells. In vivo efficacy was examined in an athymic nude mouse AtT-20 xenograft model. SAHA efficacy against human-derived corticotroph tumor (hCtT) (n = 8) was tested in vitro. National Institutes of Health. SAHA (0.5 to 8 µM). AtT-20 and hCtT cell survival, in vitro/invivo ACTH measurements. SAHA (1 µM) reduced AtT-20 viability to 75% at 24 hours, 43% at 48 hours (analysis of variance; P = 0.002). Apoptosis was confirmed with elevated BAX/Bcl2 ratio and FACS. Intriguingly, early (3-hour) significant decline (70%; P < 0.0001) of secreted ACTH and diminished POMC transcription was observed with SAHA (1 µM). Micro...Continue Reading

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References

Aug 1, 1982·Virchows Archiv. A, Pathological Anatomy and Histology·C K LeungR P Shiu
Jul 1, 1997·Journal of Endocrinological Investigation·A ColaoG Lombardi
Oct 17, 2001·The Journal of Clinical Investigation·M Páez-PeredaG K Stalla
Jan 14, 2003·Nature Medicine·Sean B JosephPeter Tontonoz
Apr 27, 2005·International Journal of Radiation Oncology, Biology, Physics·Prakash ChinnaiyanPaul M Harari
May 18, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Constantine S MitsiadesNicholas Mitsiades
Sep 8, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Purva BaliKapil Bhalla
Mar 3, 2006·The Journal of Clinical Investigation·Noam Zelcer, Peter Tontonoz
Jun 3, 2006·Endocrinology·Victor CastilloEduardo Arzt
Sep 7, 2006·Nature Reviews. Drug Discovery·Jessica E BoldenRicky W Johnstone
Dec 7, 2007·The Journal of Clinical Endocrinology and Metabolism·Chirag G PatilEdward R Laws
Apr 17, 2008·The Journal of Clinical Endocrinology and Metabolism·B M K BillerM Boscaro
Oct 2, 2008·Nature Reviews. Drug Discovery·Aleksey G Kazantsev, Leslie M Thompson
Nov 28, 2008·Molecular Endocrinology·Shunichi MatsumotoMasatomo Mori
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jan 5, 2011·The Journal of Clinical Endocrinology and Metabolism·R N ClaytonP W Jones
Jun 15, 2011·Molecular and Cellular Endocrinology·Qin-Yun MaHuai-Dong Song
Nov 23, 2011·The Journal of Clinical Investigation·Hidenori FukuokaShlomo Melmed
Mar 9, 2012·The New England Journal of Medicine·Annamaria ColaoUNKNOWN Pasireotide B2305 Study Group
Jun 26, 2012·European Journal of Endocrinology·R A FeeldersA M Pereira
Aug 2, 2012·The Journal of Clinical Endocrinology and Metabolism·Francesca Pecori GiraldiFrancesco Cavagnini
Mar 28, 2013·The Journal of Clinical Endocrinology and Metabolism·Olaf M DekkersHenrik Toft Sørensen
May 17, 2014·Nature Reviews. Drug Discovery·Cynthia Hong, Peter Tontonoz
Oct 30, 2014·Nucleic Acids Research·Damian SzklarczykChristian von Mering
Dec 9, 2014·Nature Genetics·Martin ReinckeMasayuki Komada

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Citations

Jan 24, 2018·Frontiers in Immunology·Rebecca Ellen WawmanYe Htun Oo
Jul 27, 2018·Expert Opinion on Pharmacotherapy·Sylvère Störmann, Jochen Schopohl
Dec 12, 2018·The Journal of Clinical Endocrinology and Metabolism·Marily Theodoropoulou, Martin Reincke
Nov 27, 2018·The Journal of Endocrinology·Manuel D GaheteRaul M Luque
Oct 31, 2019·Menopause : the Journal of the North American Menopause Society·Weihui YuXuejiang Gu
Mar 24, 2020·Endocrine Reviews·Vinaya Srirangam Nadhamuni, Márta Korbonits
Apr 4, 2019·International Journal of Molecular Sciences·Wenbo Li, Zheng Sun
Feb 12, 2019·Diabetology & Metabolic Syndrome·Makoto ShiraishiMichiaki Fukui
Jun 28, 2019·European Endocrinology·Elena V VarlamovMaria Fleseriu
Oct 2, 2020·The Journal of Clinical Endocrinology and Metabolism·Dongyun ZhangAnthony P Heaney
Nov 19, 2020·The Journal of Clinical Endocrinology and Metabolism·S T Sharma
Sep 1, 2019·Neurosurgery Clinics of North America·Claire M FaltermeierManish K Aghi
Dec 4, 2020·International Journal of Molecular Sciences·Hidenori FukuokaYutaka Takahashi
Dec 29, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Hui ZhangZhihong Ye
Nov 30, 2020·Endocrine Reviews·Maria Luisa BrandiRajesh V Thakker
Jul 2, 2020·Journal of Medicinal Chemistry·Terence C S HoA Ganesan
May 15, 2021·Frontiers in Endocrinology·José Miguel Hinojosa-AmayaDaniel Cuevas-Ramos
Jul 29, 2021·Translational Vision Science & Technology·Ye ZhangUNKNOWN Handan Eye Study Group

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