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Aim To investigate the effect of JYD01, an ent-kaurane diterpenoid analog, on detaching hexokinase II (HK II) from mitochondria, and discuss the underlying mechanism of anti-gastric cancer cell proliferation. Methods MTT assay was performed to measure the effect of JYD01 on the growth capacity of human gastric cancer cell lines MGC-803 and BGC-823. The glycolysis of MGC-803 cells in response to JYD01 was analyzed using a Seahorse XFp extracellular flux analyzer by real-time measurements of the extracellular acidification rate (ECAR, indicative of glycolysis). The effect of JYD01 in mitochondrial membrane potential (MMP) and apoptosis was observed by a fluorescence microscopy. The apoptotic rate and the quantitative analysis of MMP falling of cell lines treated with JYD01 were analyzed by flow cytometry. The proteins were determined by Western blot. Results JYD01 observably inhibited the growth of MGC-803 and BGC-823 cells in a dose-dependent manner. JYD01 induced a dose-dependent detachment of HK II from mitochondria of MGC-803 cells, effectively reduced glycolysis, and caused the drop of MMP leading to the release of cytochrome c. 1, 2 and 4 μmol · L
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Objective@#To investigate the effects and the underlying mechanism of DS2, a newly synthetic analog of natural ent-kaurane diterpenoid, on the proliferation and migration capabilities of human gastric cancer cells.@*Methods@#MTT assay, colony formation assay and flow cytometry were used to measure the effects of DS2 on growth, apoptosis and cell cycle of several human gastric cancer cell lines. The function of DS2 in the migration was further detected by wound healing and transwell assays. The expression of migration related proteins were determined by western blot.@*Results@#DS2 inhibited the growth of MGC-803, SGC-7901 and HGC-27 cells in a dose dependent manner. After treatment of DS2 at a concentration of 6.25 μmol/L for 24 h, the survival rates of MGC-803, SGC-7901 and HGC-27 cells were 53.87±3.05%, 55.91±6.97% and 32.41±2.64%, respectively. However, for the normal gastric epithelial cell GES-1, no obvious growth inhibition was observed. In addition, DS2 caused significant G2/M arrest and induced apoptosis in MGC-803 cells. Furthermore, compared with the negative control, the colony formation, wound healing rate as well as the number of migrating cells of MGC-803 were significantly decreased in a dose dependent manner after DS2 treatment. DS2 induced the expression of E-cadherin, whereas β-catenin and N-cadherin levels were downregulated in MGC-803.@*Conclusion@#The new compound DS2 has a strong anti-cancer activity, and this study will help us to design and synthesize better diterpenoids derivatives.
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OBJECTIVE: To investigate inhibitory effects of jaridonin, a novel ent-kaurene diterpenoid compound isolated from Isodon rubescens, on human esophageal cancer cells growth in vitro and to understand the possible mechanisms. METHODS: After treatment for 48 h, the potential effect of jaridonin on the cell viability was examined using MTT assay. The effect of jaridonin on cytomorphology was observed by a fluorescence microscopy. The cell cycle distribution and the drop of mitochondrial membrane potential (ΔΦm) of EC-1 cells treated with jaridonin were analyzed by flow cytometry. Expressions of the p53, Bax, p21 and p27 proteins related with mitochondria apoptosis pathways were detected by Western blot. RESULTS: Jaridonin caused strong antiproliferative and apoptotic effects in HeLa, Spc-Al, HT-29, EC-1 cells. Compared with control, treatment with jaridonin induced G2/M phase cell cycle arrest and resulted in a up-regulation of p53. The expression of Bax and p21 as well as p27 is also up-regulated in EC-1 cells treated by jaridonin. Jaridonin promoted the release of cytochrome C from mitochondria to cytosol. The cleavage of caspase-3/9 in EC-1 cells was also observed. CONCLUSION: Jaridonin can significantly inhibit the growth of the cancer cells, and induce the apoptosis. The antitumor activity of jaridonin might be attributed partly to the induction of cell apoptosis through inducing cell cycle arrest and activating mitochondria pathway.
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Aim: To synthesize the ent-kaurene diterpenoid and its derivatives from natural available stevioside.Methods: The crucial pharmacophore of exo-methylene ketone was designed and the carboxyl group at C-4 was modified.The cytotoxic inhibition activities in vitro of target compounds were evaluated against human cancer cells BEL-7402,HO-8910,MCF-7 and HL-60 by a MTT method.Results and Conclusion: The struc-tures of new target compounds were identified by ~1H NMR,FT-IR and EI-MS.The preliminary experimental re-sults showed that some derivatives of ent-kaurene diterpenoid possessed fair inhibitory activity against tumor cell lines compared with that of their parent steviol.