caudatin and Liver-Neoplasms

Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine "baishouwu", which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease.

Topics: Alkylating Agents; Animals; Carcinoma, Hepatocellular; Chromatography, Liquid; Diethylnitrosamine; Disease Models, Animal; Drugs, Chinese Herbal; Glycosides; Humans; Liver Neoplasms; Male; Mice; Rats; Rats, Sprague-Dawley; Steroids; Tandem Mass Spectrometry; Tissue Distribution

In the present study, we investigated the antitumor activity of caudatin in the human hepatoma cell line SMMC‑7721 by analysis of cell viability, cell cycle distribution, apoptosis and metastasis. The results showed that caudatin impaired the cell viability and inhibited the growth of SMMC-7721 cells in a time- and dose-dependent manner and resulted in cell cycle arrest in the G2 phase. In addition, SMMC-7721 cells, treated with caudatin exhibited typical characteristics of apoptosis. Furthermore, caudatin treatment resulted in a decrease in β-catenin and GSK3β in SMMC-7721 cells, with a concomitant reduction in metastatic capability and expression of Wnt signaling pathway targeted genes including cox-2, mmp-2 and mmp-9. Our findings revealed that caudatin inhibits human hepatoma cell growth and metastasis by targeting the GSK3β/β-catenin pathway and suppressing VEGF production.

Topics: Apoptosis; beta Catenin; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Glycosides; Humans; Liver Neoplasms; Neoplasm Metastasis; Steroids; Wnt Signaling Pathway