Aim Hypoxia-inducible factor 1 （HIF-1） , a heterodimeric transcription factor that mediates the adap- tation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a poten...Aim Hypoxia-inducible factor 1 （HIF-1） , a heterodimeric transcription factor that mediates the adap- tation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a potential therapeutic target. Kamebakaurin is a diterpenoid compound isolated from Isodonexcia （Maxin.） Hara, which has been used for anti-inflammatory activities. But its antitumor activity has not been reported. Kamebakaurin showed the potent inhibitory activity against HIF-1 activation by COC12 induced hypoxia in various human cancer cell lines. This compound significantly decreased the hypoxia-induced accumulation of HIF-lot protein, whereas it did not af- fect the expressions of topoisomerase-I （Topo-I）. Further analysis revealed that kamebakaurin inhibited HIF-lα protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-lα protein. Fur- thermore, kamebakaurin prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor （VEGF） and erythropoietin （EPO）. However, kamebakaurin caused cell growth inhibition via cell cycle ar- rest at G1 in tumor cells. In vivo studies, we further confirmed the inhibitory effect of kamebakaurin on the expres- sion of HIF-lα proteins, leading to a decrease growth of HCT116 cells in a xenograft tumor model. These resultsshow that kamebakaurin is an effective inhibitor of HIF-1 and provide new perspectives into its anticancer activity.展开更多
In this paper, we report the first stereo-, regio-, and chemo-selective conversion of oridonin (1) from kamebakaurin (3). The overall yield in 7 steps is 9%.
For the efficient extraction of kamebakaurin（KA）, the ultrasound-assisted extraction（UAE） of KA from Rabdosia excisa（R, excisa） via response surface methodology（RSM） was investigated with high-performance liqu...For the efficient extraction of kamebakaurin（KA）, the ultrasound-assisted extraction（UAE） of KA from Rabdosia excisa（R, excisa） via response surface methodology（RSM） was investigated with high-performance liquid chromatography（HPLC）. Effects of the experimental parameters such as extraction solvent, ratio of liquid to plant material, extraction time and extraction temperature on the extracting efficiency of KA from R. excisa were evaluated, and the purity of KA in residual was calculated. The optimized conditions were 65.5%（volume fraction） acetone, 35 ℃, time of 24.6 min with ultrasound of 80 W/L, 40 kHz, ratio of liquid to plant material at 30：1（mL/g）. The maximum yield of KA is 0.708 mg/kg, with mean purity of 6.09%, indicating that ultrasound-assisted extraction is a feasible and useful method for extracting KA from R. excisa.展开更多
文摘Aim Hypoxia-inducible factor 1 （HIF-1） , a heterodimeric transcription factor that mediates the adap- tation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a potential therapeutic target. Kamebakaurin is a diterpenoid compound isolated from Isodonexcia （Maxin.） Hara, which has been used for anti-inflammatory activities. But its antitumor activity has not been reported. Kamebakaurin showed the potent inhibitory activity against HIF-1 activation by COC12 induced hypoxia in various human cancer cell lines. This compound significantly decreased the hypoxia-induced accumulation of HIF-lot protein, whereas it did not af- fect the expressions of topoisomerase-I （Topo-I）. Further analysis revealed that kamebakaurin inhibited HIF-lα protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-lα protein. Fur- thermore, kamebakaurin prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor （VEGF） and erythropoietin （EPO）. However, kamebakaurin caused cell growth inhibition via cell cycle ar- rest at G1 in tumor cells. In vivo studies, we further confirmed the inhibitory effect of kamebakaurin on the expres- sion of HIF-lα proteins, leading to a decrease growth of HCT116 cells in a xenograft tumor model. These resultsshow that kamebakaurin is an effective inhibitor of HIF-1 and provide new perspectives into its anticancer activity.
文摘In this paper, we report the first stereo-, regio-, and chemo-selective conversion of oridonin (1) from kamebakaurin (3). The overall yield in 7 steps is 9%.
基金the National Natural Science Foundation of China，the Postdoctoral Foundation of Jiangsu Province,China，the China Postdoctoral Science Foundation
文摘For the efficient extraction of kamebakaurin（KA）, the ultrasound-assisted extraction（UAE） of KA from Rabdosia excisa（R, excisa） via response surface methodology（RSM） was investigated with high-performance liquid chromatography（HPLC）. Effects of the experimental parameters such as extraction solvent, ratio of liquid to plant material, extraction time and extraction temperature on the extracting efficiency of KA from R. excisa were evaluated, and the purity of KA in residual was calculated. The optimized conditions were 65.5%（volume fraction） acetone, 35 ℃, time of 24.6 min with ultrasound of 80 W/L, 40 kHz, ratio of liquid to plant material at 30：1（mL/g）. The maximum yield of KA is 0.708 mg/kg, with mean purity of 6.09%, indicating that ultrasound-assisted extraction is a feasible and useful method for extracting KA from R. excisa.
