Anticancer effect of caudatin in diethylnitrosamine‑induced hepatocarcinogenesis in rats

Abstract

an overwhelming endoplasmic reticulum stress (erS) and the following unfolded protein response (uPr) can induce hepatic inflammation, fibrosis and hepatocellular carcinoma (Hcc). caudatin, one of the species of c-21 steroidal glycosides mainly isolated from the roots of Cynanchum bungei Decne, exhibits potent anticancer activities in vivo. However, the effect of caudatin on Hcc remains unclear. in the present study, a diethylnitrosamine (den)-induced Hcc model was established. Nodules and tumors in rat livers were monitored by T2-/T1-weighted-magnetic resonance imaging (MRI) using a 1.5 T scanner. Caudatin reduced the number and size of nodules and alleviated the inflammatory foci in the liver. In addition, the hepatic pro-inflammatory levels of interleukin (il) 6, monocyte chemoattractant protein 1 and il-1β were decreased in caudatin-treated rats. The den-induced surge in malondialdehyde, aspartate aminotransferase, alanine transaminase and TBil were alleviated following caudatin treatment. The expression of erS chaperones glucose-regulated protein, 94 kda, glucose-regulated protein, 78 kda and protein disulfide-isomerase A4 and the proliferation marker Ki-67 in liver nodules were all downregulated by caudatin as demonstrated by immunohistochemistry, reverse transcription-quantitative PCR and western blot analysis. Caudatin reduced the cytoprotective erS sensor activating transcription factor 6-mediated signal transduction and inhibited the PKr-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 pathway. However, the effect of caudatin on inositol requiring enzyme 1 signaling was negligible. In conclusion, restoration of the dysregulated uPr program was involved in the antitumor efficacy of caudatin without inducing cumulative hepatotoxicity.

Cynanchum auriculatum Royle ex Wight., Cynanchum bungei Decne. and Cynanchum wilfordii (Maxim.) Hemsl.: Current Research and Prospects

“…As we all know, common chemical constituents are often isolated from plants that have close relationships with each other, which can reveal their chemotaxonomic significance to some extent. For example, caudatin, 2,4-dihydroxyacetophenone, 2,5-dihydroxyacetophenone, 4-hydroxyacetophenone, and baishouwubenzophenone were all isolated from CA , CB and CW , indicating there were close relationships among them [ 24 , 25 , 26 , 27 , 28 , 29 ]. C 21 -steroids (deacylmetaplexigenin, rostratamine, wilfoside C1G, cynanauriculoside E, kidjoranin, cyanoauriculoside A, wilfoside M1N), acetophenones (cynandione A–B, cynandione E), and other compounds (leucanthemitol, suceinie acid, sucrose, methyleugenol) were all obtained from CA and CW , which might strengthen the relationship between them [ 5 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”

“…To start with, as to hepatic carcinoma, a study revealed that hepatocellular mice induced by diethylnitrosamine model were subjected to the treatment of caudatin of CA at the dose of 50 mg/kg, resulting in liver nodule being reduced, and the inflammatory lesion was attenuated obviously, and the further study revealed that restoration of the dysregulated unfolded protein response was responsible for the anti-hepatoma effect of caudatin [ 25 ]. In vitro assay, caudatin-2,6-dideoxy-3- O -methy-β- d -cymaropyranoside and caudatin isolated from CA during the dose of 0.48–300 μM were able to exhibit suppressive effects on SMMC7721 cells with IC 50 values of 13.49 and 24.95 μM, respectively [ 92 ].…”

Hsa_circ_0060927 participates in the regulation of Caudatin on colorectal cancer malignant progression by sponging miR‐421/miR‐195‐5p

“…Caudatin is extracted from cynanchum auriculatum and plays a repressive role in cancer progression. 4 , 5 Thus, the study on the effects and mechanism of Caudatin in CRC progression is worthy and important to develop therapeutic strategies for CRC.…”

“…At present, more and more people are diagnosed with CRC, which poses a heavy financial burden to the sufferers, particularly to those from poor households. Caudatin is extracted from cynanchum auriculatum and plays a repressive role in cancer progression 4,5 . Thus, the study on the effects and mechanism of Caudatin in CRC progression is worthy and important to develop therapeutic strategies for CRC.…”

“…Caudatin is extracted from cynanchum auriculatum and plays a repressive role in cancer progression. 4,5 Thus, the study on the effects and mechanism of Caudatin in CRC progression is worthy and important to develop therapeutic strategies for CRC.Circular RNA (circRNA) is an endogenous transcript with a closed-loop structure. [6][7][8] CircRNA commonly acts as a competing endogenous RNA to sponge microRNA (miRNA).…”