Danazol is a synthetic anabolic steroid with properties of inhibition of interleukin-1 and TNF-α production[1]. Danazol has antigonadotrophic effects, suppressing follicle-stimulating hormone and luteinizing hormone at the hypothalamic-pituitary level, and Danazol is an impeded androgen with anabolic and attenuated masculinizing properties[2]. Danazol has been widely used to alter red cell membranes directly to increase the surface area, enhancing the resistance to osmotic lysi[3].
In vitro, Danazol treatment for 48 hours significantly inhibited the viability of MDAMB-231 and MCF-7 cells, with IC50 values of 65μM and 31μM, respectively[4]. Treatment with 100μM Danazol for 24 hours reduced the proliferation of human umbilical vein endothelial cells (HUVECs) and decreased the formation of tubular structures[5]. 30μM Danazol treatment for 72 hours induced a cell cycle arrest in Mcf10A cells, decreased mitochondrial membrane potential, and promoted the downregulation of energy metabolism transcripts[6].
In vivo, Danazol, administered at an oral dose of 100mg/kg (5 times a week) significantly prolonged survival of female lupus MRL/MpJ mice and decreased serum amyloid protein (SAP) levels during the 200-day experiment[7]. Consecutively administered intraperitoneal injection of Danazol (4mg/kg/day) for 6 days, extended the survival of mice undergoing allogeneic cardiac grafts and maintained the generation of regulatory CD4+ cells in mice[8]. Subcutaneous injection of Danazol (25mg/kg), three times a week for 4 weeks, inhibited the progression of endometriosis in the female nude mouse model of endometriosis and led to the formation of fibrotic and avascular lesions[9].
References:[1] Jaime-Pérez J C, Colunga-Pedraza P R, Gómez-Ramírez C D, et al. Danazol as first-line therapy for aplastic anemia[J]. Annals of hematology, 2011, 90(5): 523-527.
[2] Letchumanan P, Thumboo J. Danazol in the treatment of systemic lupus erythematosus: a qualitative systematic review[C]//Seminars in arthritis and rheumatism. WB Saunders, 2011, 40(4): 298-306.
[3] Ahn Y S, Fernandez L F, Kim C I, et al. Danazol therapy renders red cells resistant to osmotic lysis 1[J]. The FASEB journal, 1989, 3(2): 157-162.
[4] Deka S J, Roy A, Ramakrishnan V, et al. Danazol has potential to cause PKC translocation, cell cycle dysregulation, and apoptosis in breast cancer cells[J]. Chemical biology & drug design, 2017, 89(6): 953-963.
[5] Thomas G W, Rael L T, Shimonkevitz R, et al. Effects of danazol on endothelial cell function and angiogenesis[J]. Fertility and sterility, 2007, 88(4): 1065-1070.
[6] Irgebay Z, Yeszhan B, Sen B, et al. Danazol alters mitochondria metabolism of fibrocystic breast Mcf10A cells[J]. The Breast, 2017, 35: 55-62.
[7] Connolly K M, Stecher V J, Snyder B W, et al. The effect of danazol in the MRL/lpr mouse model of autoimmune disease[J]. Agents and Actions, 1988, 25(1): 164-170.
[8] Uchiyama M, Jin X, Zhang Q, et al. Danazol induces prolonged survival of fully allogeneic cardiac grafts and maintains the generation of regulatory CD4+ cells in mice[J]. Transplant International, 2012, 25(3): 357-365.
[9] Ngô C, Chéreau C, Nicco C, et al. Reactive oxygen species controls endometriosis progression[J]. The American journal of pathology, 2009, 175(1): 225-234.