Carbidopa (hydrate) is an aryl hydrocarbon receptor (AhR) agonist that inhibits pancreatic cancer cell and tumor growth [1]. Carbidopa can block the conversion of levodopa to dopamine in the periphery, enabling greater availability of dopamine to the central nervous system as well as minimizing the peripheral side effects of dopamine [2]. Carbidopa has been widely used to improve neurodegenerative diseases and promote the proteasomal degradation of androgen receptor (AR) protein[3].
In vitro, Carbidopa treatment for 72 hours significantly reduced the viability of NCI-H146, NCI-H209 and NCI-H727 cells, with IC50 values of 12, 22 and 29μM, respectively[4]. Treatment with 1mM Carbidopa for 24 hours significantly reduced the expression of IDO1 mRNA and IDO1 protein in BxPC-3 cells[5]. Treatment with 300μM Carbidopa for 24 hours significantly reduced the mitochondrial membrane potential of MDA-MB-231 cells, leading to mitochondrial dysfunction and cell damage[6].
In vivo, Carbidopa treatment via intraperitoneal injection at a dose of 7.5mg/kg), twice a day for 14 days, significantly inhibited tumor growth in a MCF7 cell-xenograft mouse model, and led to an increase in CYP1A1 protein and a decrease in ERα protein in the tumor tissue[7]. Daily intraperitoneal injection of Carbidopa (25mg/kg) was administered for 11 weeks, which significantly inhibited tumor growth in a xenograft mouse model of LNCaP cells and suppressed the production of serum prostate-specific antigen (PSA)[8].
References:
[1] Safe S. Carbidopa: a selective Ah receptor modulator (SAhRM)[J]. Biochemical Journal, 2017, 474(22): 3763-3765.
[2] Lenka A, Vernino S. Carbidopa: beyond Parkinson’s disease[J]. Clinical Autonomic Research, 2025, 35(3): 347-352.
[3] Chen Z, Cai A, Zheng H, et al. Carbidopa suppresses prostate cancer via aryl hydrocarbon receptor-mediated ubiquitination and degradation of androgen receptor[J]. Oncogenesis, 2020, 9(5): 49.
[4] Gilbert J A, Frederick L M, Pobst L J, et al. Hydrogen peroxide degradation and selective carbidopa-induced cytotoxicity against human tumor lines[J]. Biochemical pharmacology, 2005, 69(8): 1159-1166.
[5] Korac K, Rajasekaran D, Sniegowski T, et al. Carbidopa, an activator of aryl hydrocarbon receptor, suppresses IDO1 expression in pancreatic cancer and decreases tumor growth[J]. Biochemical Journal, 2022, 479(17): 1807-1824.
[6] Actis Dato A B, Naso L G, Martínez V R, et al. Carbidopa and ZnCarbidopa Induce Reductive Stress in MDA‐MB‐231 Cells[J]. ChemPlusChem, 2025, 90(3): e202400596.
[7] Chen Z, Xia X, Chen H, et al. Carbidopa suppresses estrogen receptor-positive breast cancer via AhR-mediated proteasomal degradation of ERα[J]. Investigational New Drugs, 2022, 40(6): 1216-1230.
[8] Wafa L A, Cheng H, Plaa N, et al. Carbidopa abrogates L‐dopa decarboxylase coactivation of the androgen receptor and delays prostate tumor progression[J]. International journal of cancer, 2012, 130(12): 2835-2844.
Carbidopa (hydrate)是一种aryl hydrocarbon receptor (AhR)激动剂，可抑制胰腺癌细胞和肿瘤的生长[1]。Carbidopa能阻断左旋多巴在外周转化为多巴胺，使多巴胺更多地进入中枢神经系统，同时最大限度地减少多巴胺的外周副作用[2]。Carbidopa已被广泛用于改善神经退行性疾病，并促进雄激素受体蛋白的蛋白酶体降解[3]。
在体外，Carbidopa处理72小时显著降低了NCI-H146、NCI-H209和NCI-H727细胞的活力，IC50值分别为12、22和29μM[4]。使用1mM的Carbidopa处理BxPC-3细胞24小时，显著降低了IDO1 mRNA和IDO1蛋白的表达[5]。使用300μM的Carbidopa处理MDA-MB-231细胞24小时，显著降低了细胞的线粒体膜电位，导致线粒体功能障碍和细胞损伤[6]。
在体内，每日两次腹腔注射7.5mg/kg剂量的Carbidopa，持续14天，显著抑制了MCF7细胞异种移植小鼠模型中的肿瘤生长，并导致肿瘤组织中CYP1A1蛋白增加和ERα蛋白减少[7]。每日腹腔注射25mg/kg的Carbidopa，持续11周，显著抑制了LNCaP细胞异种移植小鼠模型中的肿瘤生长，并抑制了血清前列腺特异性抗原（PSA）的产生[8]。