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.
Highlights
Stellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population
ESC-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
Materials and reagents RPMI-1640 medium, fetal bovine serum (FBS), penicillinstreptomycin and trypsin- ethylenediaminetetraacetic acid (EDTA)were purchased from Gibco (Grand Island, NY, USA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), dimethyl sulfoxide (DMSO) and protamine were provided by Sigma Chemical Co
Summary
Stellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. 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. In vitro cytotoxicity experiment is the first step for screening or discovery of anti-tumor drug It has the advantages of reducing substantially the amount of test drugs, determining the tumor specificity of the test drugs, simple experiment, low cost, etc. It is adopted as the approach for pharmacological researchers to tracing active ingredients or fractions of most anti-tumor nature demands a large number of experimental animals and the test samples, consuming large amounts of time and manpower. A large number of research results showed that HFA was an effective method to quickly research pharmacodynamics (e.g., Pervilleines B and C [4], Paclitaxel and Pacliex [5], C1311 and SJG-13 [6], ASI-145 [7], YSL [8], TAS-102 [9]) and mechanism (e.g., PCNA and Rb [10], p16 [11], NF-kappa B [12]) of antitumor drugs
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