Telocinobufagin (Telobufotoxin) is a cardenolide compound isolated from toad skin secretions. Telocinobufagin exerts its biological functions by inhibiting multiple signaling pathways, including STAT3, JAK2/STAT3, LARP1-mTOR, PI3K/Akt/Snail, and PLK1[1-2]. Telocinobufagin can be used in research related to various cancers, renal fibrosis, and analgesia[3-4].
In vitro, 4T1 breast cancer cells were treated with Telocinobufagin (0.05-1.5μg/ml) for 24-48 hours. By inhibiting the PI3K/Akt/ERK/Snail signaling pathway, Telocinobufagin significantly inhibited the migration and invasion capabilities of the cells[5]. CAL-62 undifferentiated thyroid carcinoma cells were treated with Telocinobufagin (0-2μg/mL) for 24 hours. By downregulating the expression of LARP1 and the activity of the mTOR signaling pathway, Telocinobufagin significantly inhibited the proliferation, migration, invasion, and adhesion capabilities of the cells[6].
In vivo, wild-type (WT) and heterozygous NKAα-1+/- mice were subjected to continuous intraperitoneal infusion of Telocinobufagin (0.1mg/kg/day) via osmotic minipumps for 4 weeks. Telocinobufagin infusion led to a significant increase in proteinuria and elevated plasma cystatin C levels, and induced mild to moderate periglomerular and peritubular fibrosis in the renal cortex of WT mice, whereas renal function impairment and fibrosis were significantly attenuated in NKAα-1+/- mice[7]. In acute pain model Swiss Webster mice, a single administration of Telocinobufagin (0.1-4mg/kg; intraperitoneal injection; or 0.1-40mg/kg; oral) was performed. Telocinobufagin demonstrated dose-dependent potent antinociceptive activity, inhibiting over 90% of nociceptive responses at the highest tested dose, with a potency approximately 4 times that of morphine[8].
References:
[1] Cao Y, Song Y, An N, et al. The effects of telocinobufagin isolated from Chan Su on the activation and cytokine secretion of immunocytes in vitro. Fundam Clin Pharmacol. 2009 Aug;23(4):457-64.
[2] Ma X, Xu W, Jin X, et al. Telocinobufagin inhibits osteosarcoma growth and metastasis by inhibiting the JAK2/STAT3 signaling pathway. Eur J Pharmacol. 2023 Mar 5;942:175529.
[3] 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. Eur J Pharmacol. 2012 Oct 5;692(1-3):19-28.
[4] Khalaf FK, Tassavvor I, Mohamed A, et al. Epithelial and Endothelial Adhesion of Immune Cells Is Enhanced by Cardiotonic Steroid Signaling Through Na+/K+-ATPase-α-1. J Am Heart Assoc. 2020 Feb 4;9(3):e013933.
[5] Gao Y, Shi L, Cao Z, et al. Telocinobufagin inhibits the epithelial-mesenchymal transition of breast cancer cells through the phosphoinositide 3-kinase/protein kinase B/extracellular signal-regulated kinase/Snail signaling pathway. Oncol Lett. 2018 May;15(5):7837-7845.
[6] Qiang LZ, Fang SZ. Telocinobufagin suppresses malignant metastasis of undifferentiated thyroid carcinoma via modulation of the LARP1-mTOR pathway. Kaohsiung J Med Sci. 2025 Mar;41(3):e12934.
[7] Kennedy DJ, Khalaf FK, Sheehy B, et al. Telocinobufagin, a Novel Cardiotonic Steroid, Promotes Renal Fibrosis via Na⁺/K⁺-ATPase Profibrotic Signaling Pathways. Int J Mol Sci. 2018 Aug 29;19(9):2566.
[8] Feitosa GIMC, Carvalho IF, Coelho EBS, et al. Potent nonopioid antinociceptive activity of telocinobufagin in models of acute pain in mice. Pain Rep. 2019 Oct 8;4(6):e791.
Telocinobufagin (Telobufotoxin)是一种从蟾蜍皮肤分泌物中分离的强心甾类化合物。Telocinobufagin通过抑制STAT3、JAK2/STAT3、LARP1-mTOR、PI3K/Akt/Snail和PLK1等多条信号通路来发挥生物学功能[1-2]。Telocinobufagin可用多种癌症、肾脏纤维化和镇痛等相关研究[3-4]。
在体外，Telocinobufagin（0.05-1.5μg/ml）处理4T1乳腺癌细胞24-48小时。Telocinobufagin通过对PI3K/Akt/ERK/Snail信号通路的抑制，显著抑制了细胞的迁移和侵袭能力[5]。Telocinobufagin（0-2μg/mL）处理CAL-62未分化甲状腺癌细胞24小时，Telocinobufagin通过下调LARP1的表达和mTOR信号通路的活性，显著抑制了细胞的增殖、迁移、侵袭和粘附能力[6]。
在体内，Telocinobufagin（0.1mg/kg/day）通过渗透性微型泵对野生型（WT）及NKAα-1+/-基因型小鼠进行为期4周的腹腔持续输注。Telocinobufagin可导致野生型小鼠出现显著的蛋白尿增加和血浆胱抑素C水平升高，并引发轻至中度的肾脏皮质肾小球及肾小管周围纤维化，而NKAα-1+/-小鼠的肾功能损伤和纤维化则被显著减弱[7]。Telocinobufagin（0.1-4mg/kg；腹腔注射；或0.1-40mg/kg；口服）单次给药处理急性疼痛模型Swiss Webster小鼠。Telocinobufagin显示出剂量依赖性的强效抗伤害感受活性，在最高测试剂量下能抑制90%以上的伤害性反应，效力约为吗啡的4倍[8]。