Dihydroisotanshinone I is a phenanthrenequinone derivative isolated from the roots of Salvia trijuga, with antioxidant effects [1]. Dihydroisotanshinone I induces ferroptosis in endometrial cancer cells by down-regulating the expression of GPX4, and inhibits the phosphorylation of STAT3 while promoting the reduction of STAT3 protein levels[2]. Dihydroisotanshinone I has been widely used to inhibit the progression of cancer cells, impede the migration ability of cancer cells, and induce DNA damage[3].
In vitro, Dihydroisotanshinone I treatment for 48 hours significantly inhibited the proliferation of A549 cells and H460 cells, with IC50 values of 15.487μM and 19.389μM, respectively[4]. Treatment with 10μM Dihydroisotanshinone I for 48 hours significantly induced apoptosis in HCT 116 cells and decreased the expression of Skp2 protein[5]. Treatment with 5μM Dihydroisotanshinone I for 4 hours significantly induced the expression of Caspase-3 and Caspase-8 in Detroit 562 cells, and increased the phosphorylation levels of ERK1/2, p38 and JNK [6].
In vivo, the 30mg/kg dose of Dihydroisotanshinone I was intraperitoneally injected every two days for 2 weeks, which significantly inhibited the tumor growth in the MCF-7 cell-xenograft mouse models[7]. Intraperitoneal injection of Dihydroisotanshinone I at a dose of 30mg/kg every two days for 18 days significantly inhibited tumor growth in the A549 cell xenograft mouse model without affecting the body weight of the mice[8].
References:
[1] Ip S P, Yang H, Sun H D, et al. Dihydroisotanshinone I protects against menadione-induced toxicity in a primary culture of rat hepatocytes[J]. Planta medica, 2002, 68(12): 1077-1081.
[2] Wu C Y, Yang Y H, Lin Y S, et al. Induction of ferroptosis and apoptosis in endometrial cancer cells by dihydroisotanshinone I[J]. Heliyon, 2023, 9(11).
[3] Lee I Y, Lin Y Y, Yang Y H, et al. Dihydroisotanshinone I combined with radiation inhibits the migration ability of prostate cancer cells through DNA damage and CCL2 pathway[J]. BMC Pharmacology and Toxicology, 2018, 19(1): 5.
[4] Wu C Y, Cherng J Y, Yang Y H, et al. Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells[J]. Oncotarget, 2017, 8(53): 90925.
[5] Lin Y Y, Lee I Y, Huang W S, et al. Danshen improves survival of patients with colon cancer and dihydroisotanshinone I inhibit the proliferation of colon cancer cells via apoptosis and skp2 signaling pathway[J]. Journal of Ethnopharmacology, 2017, 209: 305-316.
[6] Hsu C M, Yang M Y, Tsai M S, et al. Dihydroisotanshinone I as a treatment option for head and neck squamous cell carcinomas[J]. International Journal of Molecular Sciences, 2021, 22(16): 8881.
[7] Lin Y S, Shen Y C, Wu C Y, et al. Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells[J]. Frontiers in pharmacology, 2019, 10: 1226.
[8] Wu C Y, Yang Y H, Lin Y S, et al. Dihydroisotanshinone I induced ferroptosis and apoptosis of lung cancer cells[J]. Biomedicine & Pharmacotherapy, 2021, 139: 111585.
Dihydroisotanshinone I是一种从Salvia trijuga根部分离得到的菲醌衍生物，具有抗氧化作用[1]。Dihydroisotanshinone I通过下调GPX4的表达诱导子宫内膜癌细胞发生铁死亡，并抑制STAT3的磷酸化同时促进STAT3蛋白水平的降低[2]。Dihydroisotanshinone I已被广泛用于抑制癌细胞进展、阻碍癌细胞迁移能力并诱导DNA损伤[3]。
在体外，Dihydroisotanshinone I处理48小时显著抑制了A549细胞和H460细胞的增殖，IC50值分别为15.487μM和19.389μM[4]。使用10μM的Dihydroisotanshinone I处理HCT 116细胞48小时，显著诱导细胞凋亡并降低Skp2蛋白的表达[5]。使用5μM的Dihydroisotanshinone I处理Detroit 562细胞4小时，显著诱导Caspase-3和Caspase-8的表达，并增加ERK1/2、p38和JNK的磷酸化水平[6]。
在体内，每两天腹腔注射30mg/kg剂量的Dihydroisotanshinone I，持续2周，显著抑制了MCF-7细胞异种移植小鼠模型中的肿瘤生长[7]。每两天腹腔注射30mg/kg剂量的Dihydroisotanshinone I，持续18天，显著抑制了A549细胞异种移植小鼠模型中的肿瘤生长，且未影响小鼠体重[8]。