ABSTRACT
This research explored the synergistic effects and the mechanism of parthenolide (PTL) and vorinostat (suberoylanilide hydroxamic acid, SAHA) on the proliferation of A549 non-small cell lung cancer cells. The combination effect of PTL and SAHA was detected by cell counting kit-8 (CCK-8) and colony formation assays. Scratch test was performed to detect cell migration. Annexin V-fluorescein isothiocyanate isomer/propidium iodide (FITC/PI) flow cytometry and Western blot analyses were used to determine cell apoptosis and its mechanism. The results showed that combination of PTL and SAHA inhibited the proliferation and migration of A549 with a synergistic effect compared to the single-drug groups. The combination of PTL and SAHA had synergistic effect to induce cell apoptosis by regulating p53 and c-myc pathways, and affected the expression levels of poly ADP-ribose polymerase (PARP), cysteinyl aspartate specific proteinase (caspase)-9, and caspase-3. Taken together, this study shows that combination of PTL and SAHA has synergistic effect, induces cell apoptosis and inhibits A549 proliferation, which is likely to be a novel strategy for the treatment of non-small cell lung cancer.
ABSTRACT
Objective::Camptosorus sibiricus is a kind of herbal medicine and famous folk medicine. However, the bioactivities or pharmacological effects of the C. sibiricus remain to be unclear. Therefore, it is necessary to make a systematic study on chemical constituents from C. sibiricus, so as to further study its potential medicinal value, and provide certain chemical basis and foundation for the comprehensive development and the search for pharmacological activity. Method::Various column chromatographic technologies, (silica gel, Sephadex LH-20 and ODS column chromatography) as well as HPLC were adopted to separate chemical constituents of C. sibiricus extract. The structure of the purified compounds was elucidated by nuclear magnetic resonance (NMR) and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). Result::Totally 10 compounds have been isolated from water extract of C. sibiricus. By spectroscopic methods, they were elucidated as 7-dien-3-on-9-O-β-D-glucoside (1), bridelionoside F (2), (3R, 5S, 6S, 7E, 9S)-megastigm, an-7-ene-3, 5, 6, 9-tetrol 9-O-β-D-glucopyranoside (3), (6S, 7E, 9R)-roseoside (4), (3S, 5S, 6R, 9R)-3-hydroxy-5, 6-epoxy-β-ionol-9-O-β-glucopyranoside (5), 6, 9-dihydroxy-4, 7-megastigmadien-3-one (6), (3R, 6R, 7E, 9R)-3, 9-dihydroxy-4, elaphoside A (7), ptelatoside-A (8), n-butyl-a-β-D-fructofuranoside (9), dibutylphthalate(10)based on physical and chemical properties. Conclusion::All compounds were obtained from C. sibiricus for the first time. The discovery of these compounds further enriched the chemical constituents of C. sibiricus, and provided experimental and scientific basis for the comprehensive development and utilization of C. sibiricus.