Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay

Abstract

BackgroundStellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. In our previous study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2 had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC-2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor active fraction of ESC might exist in ESC-2. Here, we further observe the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo.MethodsIn this study, we used hollow fiber tumor model to evaluate the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic rates of the cancer cells retrieved from the hollow fibers were measured with flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-α expression were determined with elisa assay and radioimmunoassay respectively.ResultsThe results showed that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the effect strength, dose and antitumor spectrum, the order of antitumor effects of ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs. ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas-L protein, but TNF-α/TNFR1 protein expression in NCI-H460 cells changed significantly after ESC and ESC-2 treatment.ConclusionESC-2 had the similar antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be the main antitumor active fraction of ESC, which was consistent with our previous results in vitro.

ESC reverses epithelial mesenchymal transition induced by transforming growth factor-β via inhibition of Smad signal pathway in HepG2 liver cancer cells

“…Many studies showed that a variety of Stellera chamaejasme L. extracts or monomers had anti-tumor activities and could induce apoptosis of tumor cells [ 7 – 10 ]. Our previous studies also got the same results [ 11 , 12 ], but there were no experiments on its anti-metastasis effects. In this study, we further observed the effects of ESC on TGF-β-mediated EMT and classical Smad-dependent signaling pathway in HepG2 liver cancer cells.…”

“…ESC, the extract of Stellera Chamaejasme L., inhibited proliferation and induced apoptosis in various tumor cells by activation apoptotic death receptor signaling pathway in our previous researches [ 11 , 12 ]. In this study, we found that EMT induced by TGF-β in HepG2 cells could be reversed by ESC (doses less than 12.5 μg/mL were used to avoid the influence of anti-proliferation of ESC).…”

Simultaneous determination of isochamaejasmin, neochamaejasmin A and aphnoretinin rat plasma by UPLC‐MS/MS and its application to a pharmacokinetic study of Stellera chamaejasme L. extract

“…Compounds obtained from S. chamaejasme L. have shown significant anticancer activities (Li, Zhang, Pang, Zheng, & Gan, 2014;Liu et al, 2014;Qian & Li, 2017). Isochamaejasmin induces apoptosis in leukemia cells by inhibiting the activity of Bcl-2 family proteins (Zhang, Abbreviations: AUC, area under the plasma concentration-time curve; C max , Maximum plasma concentration; MRT, mean residence time; QC, quality control; RE, relative error; RSD, relative standard deviation; t 1/2 , half-life; T max , time to C max ; UPLC-MS/MS, ultra-performance liquid chromatographytandem mass spectrometry.…”

A UPLC‐MS/MS method for simultaneous determination of five flavonoids from Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic study

“…Previous phytochemical studies of S. chamaejasme L. have shown that it contains various kinds of chemical components, including diterpene, lignans, coumarins, phenylpropanoid, flavonoids and volatile oil (Li, Shen, Bao, Chen, & Li, ; Yan et al, ; Zhang et al, ). Modern studies have suggested that flavonoids from S. chamaejasme L. are the main components that mostly contribute to the pharmacological efficacy (Liu et al, ; Liu & Zhu, ; Liu, Han, et al, ; Liu, Yang, et al, ), such as anti‐cancer activity (Liu et al, ; Li, Zhang, Pang, ZhengChen, & Gan, ), anti‐fatty liver (Wang, Li, Han, Wang, & Li, ) and anti‐HIV (Asada et al, ).…”

“…. Modern studies have suggested that flavonoids from S. chamaejasme L. are the main components that mostly contribute to the pharmacological efficacy Liu, Han, et al, 2014;Liu, Yang, et al, 2014), such as anti-cancer activity Li, Zhang, Pang, ZhengChen, & Gan, 2014), anti-fatty liver (Wang, Li, Han, Wang, & Li, 2015) and anti-HIV (Asada et al, 2013). effects.…”