DIM-C-pPhCO2Me is a nuclear receptor 4A1 (NR4A1) antagonist, with a Ki value of 0.25µM [1]. DIM-C-pPhCO2Me can inhibit the migration of cancer cells by inhibiting the activity of NR4A1 and increasing the mRNA and protein expression of IL24[2]. DIM-C-pPhCO2Me has been widely used to inhibit the growth of different cancer cells and induce apoptosis[3].
In vitro, DIM-C-pPhCO2Me treatment for 24 hours significantly inhibited the proliferation of ACHN cells and 786-O cells with IC50 values of 11.7μM and 13.4μM, respectively[4]. Treatment with 20µM DIM-C-pPhCO2Me for 48h inhibited Rh30 cell growth and decreased the expression of survivin, bcl-2, cyclin D1, EGFR, and cMyc in cells[5]. Treatment of 20µM DIM-C-pPhCO2Me for 24h reduced β1-integrin and α5-integrin expression in SW480 cells and inhibited cell adhesion and migration[6].
In vivo, DIM-C-pPhCO2Me treatment via gavage at a dose of 40mg/kg (every other day for 20 days) inhibited tumor growth in athymic nude mice bearing Rh30 cells as xenografts[5]. A single dose of 2mg/kg DIM-C-pPhCO2Me administered intratracheally 30min before E. coli infection significantly increased mouse survival and global protein levels in bronchoalveolar lavage fluid[7].
References:
[1] Lee S O, Li X, Hedrick E, et al. Diindolylmethane analogs bind NR4A1 and are NR4A1 antagonists in colon cancer cells[J]. Molecular endocrinology, 2014, 28(10): 1729-1739.
[2] Lacey A, Hedrick E, Cheng Y, et al. Interleukin-24 (IL24) is suppressed by PAX3-FOXO1 and is a novel therapy for rhabdomyosarcoma[J]. Molecular cancer therapeutics, 2018, 17(12): 2756-2766.
[3] Wu L, Chen L. Characteristics of Nur77 and its ligands as potential anticancer compounds[J]. Molecular medicine reports, 2018, 18(6): 4793-4801.
[4] Hedrick E, Lee S O, Kim G, et al. Nuclear receptor 4A1 (NR4A1) as a drug target for renal cell adenocarcinoma[J]. PloS one, 2015, 10(6): e0128308.
[5] Lacey A, Hedrick E, Li X, et al. Nuclear receptor 4A1 (NR4A1) as a drug target for treating rhabdomyosarcoma (RMS)[J]. Oncotarget, 2016, 7(21): 31257.
[6] Hedrick E, Lee S, Safe S. The nuclear orphan receptor NR4A1 regulates β1‐integrin expression in pancreatic and colon cancer cells and can be targeted by NR4A1 antagonists[J]. Molecular carcinogenesis, 2017, 56(9): 2066-2075.
[7] Cui P, Wu S, Xu X, et al. Deficiency of the transcription factor NR4A1 enhances bacterial clearance and prevents lung injury during Escherichia coli pneumonia[J]. Shock, 2019, 51(6): 787-794.
DIM-C-pPhCO2Me是一种核受体4A1（NR4A1）拮抗剂，Ki值为0.25µM[1]。DIM-C-pPhCO2Me能通过抑制NR4A1活性并增加IL24的mRNA和蛋白表达来抑制癌细胞的迁移[2]。DIM-C-pPhCO2Me已被广泛用于抑制不同癌细胞的生长并诱导细胞凋亡[3]。
在体外，DIM-C-pPhCO2Me 处理24小时显著抑制了ACHN细胞和786-O细胞的增殖，IC50值分别为11.7µM和13.4µM[4]。使用20µM的DIM-C-pPhCO2Me 处理48小时，抑制了Rh30细胞的生长，并降低了细胞中survivin、bcl-2、cyclin D1、EGFR和cMyc的表达[5]。使用20µM的DIM-C-pPhCO2Me处理24小时，降低了SW480细胞中β1-整合素和α5-整合素的表达，并抑制了细胞粘附和迁移[6]。
在体内，以40mg/kg的剂量通过灌胃给予DIM-C-pPhCO2Me（每隔一天一次，持续20天），抑制了携带Rh30细胞异种移植瘤的无胸腺裸鼠的肿瘤生长[5]。在大肠杆菌感染前30分钟，单次气管内给予2mg/kg剂量的DIM-C-pPhCO2Me，显著提高了小鼠的存活率，并增加了支气管肺泡灌洗液中的总蛋白水平[7]。