Bufotalin is a natural cardiotonic steroid derived from toad secretions [1]. Bufotalin inhibits Na⁺/K⁺-ATPase and induces apoptosis of cancer cells [2]. Bufotalin has potent anti-tumor and cardiotonic effects [3-4].
In R-HepG2 cells, treatment with a relatively low concentrations of Bufotalin (0.05μM, 0.125μM; 24h, 48h) induced a remarkable G2/M arrest [5]. In A375 cells, Bufotalin (10-80ng/mL; 24h) significantly inhibited cell proliferation [6]. In MDA-MB-231 cells, Bufotalin (1-10μM; 72h) inhibits the proliferation of cells in a dose-dependent manner [7].
In bleomycin-induced lung fibrosis mice model, Bufotalin (1mg/kg, 2mg/kg; ip; 7d) reduces lung injury, inflammation, and fibrosis, and protects lung function [8]. In Sjögren’s syndrome (ESS) murine model, Bufotalin (10μg/kg; iv; twice a week for 7 weeks) inhibits Th17 polarization and secretion of cytokines IL-17 and IFN-γ [9]. In mice bearing U251 cell xenografts, Bufotalin (1mg/kg, 2mg/kg, 5mg/kg; ip; 14d) treatment resulted in a significant dose-dependent decrease in tumor volume and weight [10].
References:
[1]. El-Seedi HR, Yosri N, El-Aarag B, et al. Chemistry and the potential antiviral, anticancer, and anti-inflammatory activities of cardiotonic steroids derived from toads. Molecules. 2022 Oct 5; 27(19): 6586.
[2]. Mijatovic T, Dufrasne F, Kiss R. Cardiotonic steroids-mediated targeting of the Na+/K+-ATPase to combat chemoresistant cancers. Current medicinal chemistry. 2012 Feb 1; 19(5): 627-646.
[3]. Tian H, Zhao F, Yue BS, et al. Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom. Drug Design, Development and Therapy. 2024 Dec 31:3549-3594.
[4]. Jia J, Li J, Zheng Q, et al. A research update on the antitumor effects of active components of Chinese medicine ChanSu. Frontiers in Oncology. 2022 Sep 27; 12: 1014637.
[5]. Zhang DM, Liu JS, Tang MK, et al. Bufotalin from Venenum Bufonis inhibits growth of multidrug resistant HepG2 cells through G2/M cell cycle arrest and apoptosis. European journal of pharmacology. 2012 Oct 5; 692(1-3): 19-28.
[6]. Pan Z, Qu C, Chen Y, et al. Bufotalin induces cell cycle arrest and cell apoptosis in human malignant melanoma A375 cells. Oncology reports. 2019 Apr; 41(4): 2409-2417.
[7]. Park SJ, Jung HJ. Bufotalin suppresses proliferation and metastasis of triple-negative breast cancer cells by promoting apoptosis and inhibiting the STAT3/EMT axis. Molecules. 2023 Sep 23; 28(19): 6783.
[8]. Yin JZ, Li ZQ, Zhang XD, et al. Bufotalin attenuates pulmonary fibrosis via inhibiting Akt/GSK-3β/β-catenin signaling pathway. European Journal of Pharmacology. 2024 Feb 5; 964: 176293.
[9]. Huang Y, Yang G, Fei J, et al. Bufotalin ameliorates experimental Sjögren’s syndrome development by inhibiting Th17 generation. Naunyn-Schmiedeberg's Archives of Pharmacology. 2020 Oct; 393: 1977-1985.
[10]. Tan J, Lin G, Zhang R, et al. Bufotalin induces oxidative stress-mediated apoptosis by blocking the ITGB4/FAK/ERK pathway in glioblastoma. Antioxidants. 2024 Sep 27; 13(10): 1179.
Bufotalin是一种天然的强心类固醇，来源于蟾蜍分泌物 [1]。Bufotalin可抑制Na⁺/K⁺-ATPase并诱导癌细胞凋亡 [2]。Bufotalin具有强效的抗肿瘤和强心作用 [3-4]。
在R-HepG2细胞中，较低浓度的Bufotalin（0.05μM、0.125μM；24h、48h）处理可诱导显著的G2/M期阻滞 [5]。在A375细胞中，Bufotalin（10-80ng/mL；24h）显著抑制细胞增殖 [6]。在MDA-MB-231细胞中，Bufotalin（1-10μM；72h）以剂量依赖性方式抑制细胞增殖 [7]。
在博来霉素诱导的肺纤维化小鼠模型中，Bufotalin（1mg/kg、2mg/kg；ip；7d）可减轻肺损伤、炎症和纤维化，并保护肺功能 [8]。在干燥综合征（ESS）小鼠模型中，Bufotalin（10μg/kg；iv；每周两次，持续7周）可抑制Th17极化以及细胞因子IL-17和IFN-γ的分泌 [9]。在携带U251细胞异种移植的小鼠中，Bufotalin（1mg/kg、2mg/kg、5mg/kg；ip；14d）治疗导致肿瘤体积和重量显著剂量依赖性下降 [10]。