Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C (1, named barbatin D) and 6-(2-acetoxy-3-methylbutanoloxy)-7-(2-carbonyl-3-methylbutanoyloxy) barbatin C (2, named barbatin E) were isolated from ...Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C (1, named barbatin D) and 6-(2-acetoxy-3-methylbutanoloxy)-7-(2-carbonyl-3-methylbutanoyloxy) barbatin C (2, named barbatin E) were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic methods including extensive 1 D and 2D NMR analyses. In vitro, compounds 1-2 showed cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and with IC50 values in the range of 3.5-6.7μM.展开更多
Objective: To investigate the effect of the ethanol extract of Scutellaria barbata D. Don(EESB) on colorectal cancer(CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. Methods: In vivoexperim...Objective: To investigate the effect of the ethanol extract of Scutellaria barbata D. Don(EESB) on colorectal cancer(CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. Methods: In vivoexperiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group(n=10) and control group(n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry(IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/m L EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay and colony formation assay, respectively. The m RNA expression of c-Myc, Survivin and adenomatous polyposis coli(APC) was examined by reverse transcription-polymerase chain reaction(RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting. Results: EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group(P〈0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues(P〈0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner(P〈0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells(P〈0.05). In addition, RT-PCR assay showed that EESB decreased the m RNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells(P〈0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells(P〈0.05). Conclusions: EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.展开更多
基金the National Natural Science Foundation of China (20772104).
文摘Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C (1, named barbatin D) and 6-(2-acetoxy-3-methylbutanoloxy)-7-(2-carbonyl-3-methylbutanoyloxy) barbatin C (2, named barbatin E) were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic methods including extensive 1 D and 2D NMR analyses. In vitro, compounds 1-2 showed cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and with IC50 values in the range of 3.5-6.7μM.
基金Supported by the Natural Science Foundation of Fujian Province of China(No.2013J01333)the Youth Science Foundation of the Health Department of Fujian Province(2012-2-60)the Developmental Fund of Chen Keji Integrative Medicine(No.CKJ2015008)
文摘Objective: To investigate the effect of the ethanol extract of Scutellaria barbata D. Don(EESB) on colorectal cancer(CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. Methods: In vivoexperiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group(n=10) and control group(n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry(IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/m L EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay and colony formation assay, respectively. The m RNA expression of c-Myc, Survivin and adenomatous polyposis coli(APC) was examined by reverse transcription-polymerase chain reaction(RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting. Results: EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group(P〈0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues(P〈0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner(P〈0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells(P〈0.05). In addition, RT-PCR assay showed that EESB decreased the m RNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells(P〈0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells(P〈0.05). Conclusions: EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.