Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers, associated with high mortality, and the world’s highest morbidity and mortality rates for this malignant tumor are found in China [1].Since hepatocellular carcinoma (HCC) mostly arises from chronic hepatitis and liver cirrhosis caused by infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), novel antihepatocarcinogenic agents exhibiting comprehensive effects in therapy of chronic hepatitis and prevention liver cirrhosis are required [2].The root of Cynanchum auriculatum Royle ex Wight, known as “baishouwu” in China, has been widely used in the clinic as a beneficial and tonic agent for long times
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
On account of the results, we speculated that the C-21 steroidal glycosides obtained in our work were sensitive to some human tumor cell lines such as liver cancer cell lines
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers, associated with high mortality, and the world’s highest morbidity and mortality rates for this malignant tumor are found in China [1].Since HCC mostly arises from chronic hepatitis and liver cirrhosis caused by infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), novel antihepatocarcinogenic agents exhibiting comprehensive effects in therapy of chronic hepatitis and prevention liver cirrhosis are required [2].The root of Cynanchum auriculatum Royle ex Wight, known as “baishouwu” in China, has been widely used in the clinic as a beneficial and tonic agent for long times. Several C-21 steroidal glycosides were isolated from baishouwu, of which caudatin was the most potent compound against tumor cell lines and showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines [8]. On account of the results, we speculated that the C-21 steroidal glycosides obtained in our work were sensitive to some human tumor cell lines such as liver cancer cell lines. Further in vitro studies illustrated that the anticancer activity of caudatin could be attributed partly to its inhibition of cell proliferation and induction of apoptosis in human hepatoma cell line SMMC7721 through caspase activation [9]. Recent studies proved that caudatin could induce cell cycle arrest and caspase-dependent apoptosis in HepG2 cells [10]
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