Cinobufotalin

Cinobufotalin is a steroidal glycoside with multiple biological activities^[1]. Cinobufotalin is a cardiotonic steroid or butadiene lactone extracted from the skin secretions of toads^[2]. Cinobufotalin has been used as a cardiotonic, diuretic and hemostatic drug, and also has antitumor activity^[3].

In vitro, Cinobufotalin (0.1, 1, 5, 10μM) treatment of SK-OV-3, CRL-1978 and CRL-11731 cells for 24-72h dose-dependently inhibited cell proliferation, migration and invasion^[4]. Cinobufotalin (40, 60, 80nM) was used to treat HepG2, SMMC-7721 and SNU-368 cells for 24-48h, which upregulated epithelial markers (E-cadherin), downregulated mesenchymal markers (N-cadherin, snail, slug and ZEB1), and reduced the mRNA and protein expression of β-catenin^[5].

In vivo, Cinobufotalin (1, 5mg/kg) was used to treat A549 cell xenograft mice by intraperitoneal injection for 1 week, which significantly inhibited the growth of transplanted tumors in mice and improved the survival rate of mice^[6]. Cinobufotalin (5mg/kg) was used to treat H22 liver cancer mice by intraperitoneal injection, which significantly inhibited tumor growth, enhanced the immune function of mice, and enhanced the chemotherapy effect of cisplatin^[7].

References:
[1] El-Seedi H R, Yosri N, El-Aarag B, et al. Chemistry and the potential antiviral, anticancer, and anti-inflammatory activities of cardiotonic steroids derived from toads[J]. Molecules, 2022, 27(19): 6586.
[2] Cheng C, Wang J, Chen J, et al. New therapeutic aspects of steroidal cardiac glycosides: the anticancer properties of Huachansu and its main active constituent Bufalin[J]. Cancer Cell International, 2019, 19: 1-27.
[3] Liu Q, Shu L, Wen Y, et al. Cinobufagin and cinobufotalin from Traditional Chinese Medicine and chemical synthesis[J]. Authorea Preprints, 2023.
[4] Afroze S H, Peddaboina C, MCDOWELL A B, et al. Differential effects of in vitro treatment with cinobufotalin on three types of ovarian cancer cells[J]. Anticancer Research, 2018, 38(10): 5717-5724.
[5] Li W, Pei S, Zhang X, et al. Cinobufotalin inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells through down-regulate β-catenin in vitro and in vivo[J]. European Journal of Pharmacology, 2022, 922: 174886.
[6] Kai S, Lu J, Hui P, et al. Pre-clinical evaluation of cinobufotalin as a potential anti-lung cancer agent[J]. Biochemical and biophysical research communications, 2014, 452(3): 768-774.
[7] Wang P P, Wang Y H, Wang L S, et al. Anti-tumor effect and its related mechanisms of cinobufotalin combined with cisplatin on H22 liver cancer mice[J]. Zhongguo Zhong yao za zhi= Zhongguo Zhongyao Zazhi= China Journal of Chinese Materia Medica, 2020, 45(16): 3945-3951.

Cinobufotalin是一种具有多种生物活性的甾体糖苷^[1]。Cinobufotalin是一种强心类固醇或丁二烯内酯，是从蟾蜍的皮肤分泌物中提取的^[2]。Cinobufotalin已被用作强心药，利尿药和止血药，还具有抗肿瘤活性^[3]。

在体外，Cinobufotalin（0.1, 1, 5, 10μM）处理SK-OV-3、CRL-1978和CRL-11731细胞24-72h，剂量依赖性地抑制了细胞增殖、迁移和侵袭^[4]。Cinobufotalin（40, 60, 80nM）处理HepG2、SMMC-7721和SNU-368细胞24-48h，上调了上皮标志物（E-cadherin），下调了间质标志物（N-cadherin、snail、slug和ZEB1），降低了β-catenin的mRNA和蛋白表达^[5]。

在体内，Cinobufotalin（1, 5mg/kg）通过腹腔注射治疗A549细胞异种移植小鼠1周，显著抑制了小鼠体内移植瘤的生长，提高了小鼠存活率^[6]。Cinobufotalin（5mg/kg）通过腹腔注射治疗H22肝癌小鼠，显著抑制了肿瘤生长，增强了小鼠的免疫功能，增强了顺铂的化疗效果^[7]。