Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨm) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G2/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of ΔΨm, resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G2/M phase arrest and apoptosis of T24 cells.
Liver cancer is one of the most commonly diagnosed cancers and the leading cause of death in human populations. Butein, a tetrahydroxychalcone, has been shown to induce apoptosis in many human cancer cells, but the effects of butein on the migration and invasion of human liver cancer cells are not reported. Herein, we found that butein is effective in the suppression of migration and invasion in SK-HEP-1 human hepatocarcinoma cells by using the Matrigel cell migration assay and invasion system. The gelatin zymography assay indicated that butein inhibited the activity of matrix metalloproteinases 2 (MMP-2) and MMP-9. Western blotting analysis indicated that butein decreased the levels of MMP-2, -7, and -9, uPA, Ras, Rho A, ROCK1, ERK1/2, JNK1/2, p-p38, and p-c-Jun in SK-HEP-1 cells. Furthermore, butein inhibited the NF-κB binding activity in SK-HEP-1 cells by electrophoretic mobility shift assay. We also found that butein decreased the ERK, JNK, and p38 in SK-HEP-1 cells by in vitro kinase assay. In conclusion, this is the first study to demonstrate that butein might be a novel anticancer agent for the treatment of hepatocarcinoma through inhibiting migration and invasion.
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