Bufalin is a Na+/K+-ATPase inhibitor (α1: Kd = 42.5nM; α2: Kd = 45nM; α3: Kd = 40nM) [1]. Bufalin primarily inhibits the activity of Na⁺/K⁺-ATPase on cell membranes, leading to elevated intracellular calcium concentrations [2]. Bufalin induction of apoptosis and inhibition of tumor cell proliferation can also have multiple anti-tumor mechanisms, including triggering autophagy and inhibiting tumor angiogenesis [3]. Bufalin is used to treat various tumors, including liver cancer, lung cancer, breast cancer, and leukemia [4].
In NCI-H640 cells, after treatment with Bufalin (1μM, 2μM, 4μM; 24h), the activity of cells decreased significantly [5]. In Ishikawa, SK-OV-3 and OMC-3 ovarian cancer cells, Bufalin (0.1-10ng/mL; 48h) can inhibit the proliferation of endometrial and ovarian cancer cells [6]. In human RCC ACHN cells, Bufalin (0-80nM; 12-72h) suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway [7].
In carrageenan-induced paw edema rat model, after Bufalin (0.15mg/kg, 0.3mg/kg, 0.6mg/kg; ip; single injection) treatmentthe, volume of paw edema in rats was significantly reduced [8]. In HCCLM3 cell metastatic orthotopic tumor mouse model, orthotopic transplanted tumor tissues undergo necrosis and apoptosis induced by Bufalin (1mg/kg, 1.5mg/kg; ip; 30d) treatment [9].
References:
[1]. Katz A, Lifshitz Y, Bab-Dinitz E, et al. Selectivity of digitalis glycosides for isoforms of human Na, K-ATPase[J]. Journal of Biological Chemistry, 2010, 285(25): 19582-19592.
[2]. Wu S H, Bau D T, Hsiao Y T, et al. Bufalin induces apoptosis in vitro and has Antitumor activity against human lung cancer xenografts in vivo[J]. Environmental Toxicology, 2017, 32(4): 1305-1317.
[3]. Yin P H, Liu X, Qiu Y Y, et al. Anti-tumor activity and apoptosis-regulation mechanisms of bufalin in various cancers: new hope for cancer patients[J]. Asian Pacific journal of cancer prevention, 2012, 13(11): 5339-5343.
[4]. Lan Y L, Lou J C, Jiang X W, et al. A research update on the anticancer effects of bufalin and its derivatives[J]. Oncology letters, 2019, 17(4): 3635-3640.
[5]. Wu S H, Wu T Y, Hsiao Y T, et al. Bufalin induces cell death in human lung cancer cells through disruption of DNA damage response pathways[J]. The American Journal of Chinese Medicine, 2014, 42(03): 729-742.
[6]. Takai N, Ueda T, Nishida M, et al. Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells[J]. International journal of molecular medicine, 2008, 21(5): 637-643.
[7]. Xie J, Lin W, Huang L, et al. Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway[J]. Oncology letters, 2018, 16(3): 3867-3873.
[8]. Wen L, Huang Y, Xie X, et al. Anti‐inflammatory and antinociceptive activities of bufalin in rodents[J]. Mediators of inflammation, 2014, 2014(1): 171839.
[9]. Zhang Z J, Yang Y K, Wu W Z. Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice[J]. Journal of translational medicine, 2014, 12(1): 57.
Bufalin是一种Na+/K+-ATPase抑制剂（α1：Kd = 42.5nM；α2：Kd = 45nM；α3：Kd = 40nM） [1]。Bufalin主要抑制细胞膜上Na⁺/K⁺-ATPase的活性，导致细胞内钙离子浓度升高 [2]。Bufalin诱导细胞凋亡、抑制肿瘤细胞增殖，并可能通过多种抗肿瘤机制发挥作用，包括触发自噬和抑制肿瘤血管生成 [3]。Bufalin用于治疗多种肿瘤，包括肝癌、肺癌、乳腺癌和白血病 [4]。
在NCI-H640细胞中，用Bufalin（1μM，2μM，4μM；24h）处理后，细胞的活性显著下降 [5]。在Ishikawa、SK-OV-3和OMC-3卵巢癌细胞中，Bufalin（0.1-10ng/mL；48h）可抑制子宫内膜癌和卵巢癌细胞的增殖 [6]。在人肾细胞癌ACHN细胞中，Bufalin（0-80nM；12-72h）通过抑制PI3K/Akt/mTOR信号通路抑制肾细胞癌的增殖和转移 [7]。
在角叉菜胶诱发的大鼠足跖水肿模型中，Bufalin（0.15mg/kg，0.3mg/kg，0.6mg/kg；ip；单次注射）治疗后，大鼠足跖水肿体积显著减少 [8]。在HCCLM3细胞转移性原位肿瘤小鼠模型中，Bufalin（1mg/kg，1.5mg/kg；ip；30d）治疗引起原位移植肿瘤组织坏死、凋亡 [9]。