Spironolactone is an orally active dual antagonist of the mineralocorticoid receptor (MR; IC₅₀=24nM) and androgen receptor (AR; IC₅₀=77nM)[1-2]. Spironolactone exerts potassium-sparing diuretic effects by antagonizing aldosterone and modulates hormone-related diseases through Spironolactone anti-androgenic activity. Spironolactone is applicable in research areas such as heart failure, cancer, hypertension, and female acne and androgenetic alopecia[3-4].
In vitro, pretreatment of MC3T3-E1 osteoblasts with Spironolactone (0.01–1μM) for 1 hour, followed by stimulation with Methylglyoxal (400μM) for 48 hours, Spironolactone significantly inhibited Methylglyoxal-induced cell death and apoptosis, and improved bone formation activity. Spironolactone reduced Methylglyoxal-induced endoplasmic reticulum stress, intracellular reactive oxygen species generation, mitochondrial superoxide levels, and cardiolipin peroxidation, while also suppressing the secretion of inflammatory cytokines[5]. Treatment of H295R adrenocortical cells with Spironolactone (0.1–30μM) for 24 hours, Spironolactone significantly inhibited basal cortisol and aldosterone production. Spironolactone inhibits the activity of steroidogenic enzymes[6].
In vivo, intraperitoneal administration of Spironolactone (50mg/kg body weight/day) to tumor-bearing (CSCL or SLGC cells) NOD-SCID mice (starting from day 21 post-cell inoculation, twice a week for three weeks), Spironolactone significantly inhibited tumor growth and reduced the proportion of cancer stem cells within the tumor, while inducing apoptosis in cancer cells and cancer stem cells by impairing the DNA damage response[7]. Oral gavage administration of Spironolactone (50mg/kg body weight/day) to BALB/c mice with experimental autoimmune myocarditis (starting from day 7 post-immunization, once daily for four weeks), Spironolactone significantly improved myocardial hypertrophy and diastolic function, reduced inflammatory cytokine levels, and decreased collagen deposition and myocardial fibrosis by inhibiting the TGF-β1/Smad-2/3/Ets-1 signaling pathway[8].
References:
[1] Struthers A, Krum H, Williams GH. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol. 2008 Apr;31(4):153-8.
[2] Karim A. Spironolactone: disposition, metabolism, pharmacodynamics, and bioavailability. Drug Metab Rev. 1978;8(1):151-88.
[3] Ershadi S, Barbieri JS. Spironolactone for Acne: Practical Strategies for Optimal Clinical Outcomes. Cutis. 2025 Jul;116(1):26-31.
[4] Heymann WR. Spironolactone and breast cancer: Fear not! J Am Acad Dermatol. 2020 Oct;83(4):1008-1009.
[5] Park SY, Suh KS, Jung WW, et al. Spironolactone Attenuates Methylglyoxal-induced Cellular Dysfunction in MC3T3-E1 Osteoblastic Cells. J Korean Med Sci. 2021 Oct 4;36(38):e265.
[6] Ye P, Yamashita T, Pollock DM, et al. Contrasting effects of eplerenone and spironolactone on adrenal cell steroidogenesis. Horm Metab Res. 2009 Jan;41(1):35-9.
[7] Gold A, Eini L, Nissim-Rafinia M, et al. Spironolactone inhibits the growth of cancer stem cells by impairing DNA damage response. Oncogene. 2019 Apr;38(17):3103-3118.
[8] Wang WK, Wang B, Cao XH, et al. Spironolactone alleviates myocardial fibrosis via inhibition of Ets-1 in mice with experimental autoimmune myocarditis. Exp Ther Med. 2022 Jun;23(6):369.
Spironolactone是一种具有口服活性的盐皮质激素受体（MR；IC50=24nM）和雄激素受体（AR；IC50=77nM）双重拮抗剂[1-2]。Spironolactone通过拮抗醛固酮发挥保钾利尿作用，并凭借抗雄激素活性调节激素相关疾病，Spironolactone可用于心力衰竭、癌症、高血压以及女性痤疮和雄激素源性脱发等相关研究[3-4]。
在体外，Spironolactone（0.01–1μM）预处理MC3T3-E1成骨细胞1小时，随后使用甲基乙二醛（400μM）刺激细胞48小时，Spironolactone显著抑制甲基乙二醛诱导的细胞死亡和凋亡，并改善骨形成活性。Spironolactone降低甲基乙二醛诱导的内质网应激、细胞内活性氧生成、线粒体超氧化物水平和心磷脂过氧化，同时抑制炎症因子的分泌[5]。Spironolactone（0.1–30μM）处理H295R肾上腺皮质细胞24小时，Spironolactone显著抑制基础皮质醇和醛固酮的产生。Spironolactone抑制类固醇生成酶的活性[6]。
在体内，Spironolactone（50mg/kg体重/天）腹腔注射处理荷瘤（CSCL或SLGC细胞）NOD-SCID小鼠（从接种细胞后第21天开始，每周两次，持续三周），Spironolactone显著抑制肿瘤生长并降低肿瘤内癌症干细胞比例，同时通过损害DNA损伤反应诱导癌细胞和癌症干细胞凋亡[7]。Spironolactone（50mg/kg体重/天）灌胃处理实验性自身免疫性心肌炎BALB/c小鼠（从免疫后第7天开始，每天一次，持续四周），Spironolactone显著改善心肌肥厚和舒张功能，降低炎症因子水平，并通过抑制TGF-β1/Smad-2/3/Ets-1信号通路减少胶原沉积和心肌纤维化[8]。