Petasin is a potential antitumor against human neuroblastoma cell SK-N-SH by inhibiting the ERK1/2 phosphorylation. In view of its great activity and new antiproliferative mechanisms, a series of petasin derivatives w...Petasin is a potential antitumor against human neuroblastoma cell SK-N-SH by inhibiting the ERK1/2 phosphorylation. In view of its great activity and new antiproliferative mechanisms, a series of petasin derivatives were designed and synthesized, which showed great antiproliferative activity. Among them compounds 1h and 1f were more effective against SK-N-SH cells than petasin with the IC50 values of 0.87 and 2.63 μM, respectively.展开更多
Background:Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far.Petasin,a natural product found in plants of the genus Petasites,has been reported to possess anticance...Background:Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far.Petasin,a natural product found in plants of the genus Petasites,has been reported to possess anticancer activity.The present study aimed to investigate the anticolon cancer activity of petasin both in vitro and in vivo.The molecular mechanism of petasin was also further explored.Methods:Caco-2,LoVo,SW-620,and HT-29 cell lines were used to detect the inhibitory effect of petasin on colon cancer proliferation.Cell viability was determined using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide)assay.Cell apoptosis was analyzed by flow cytometry.Hoechst 33258 staining was used to visualize morphological changes.Cell migration was assessed using a wound-healing migration assay,and cell invasion was investigated using Transwell chambers.Western blotting assays were employed to evaluate the expression levels of proteins in the protein kinase B/mammalian target of rapamycin(Akt/mTOR)signaling pathway.Finally,in vivo activity of petasin was evaluated using the SW-620 subcutaneous tumor model established in Balb/c nude mice.Twelve rats were randomly divided into control group and 10 mg/kg petasin group.The tumor volume was calculated every 7 days for 28 days.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay was performed to assess the apoptotic effect of petasin.Differences between two groups were assessed by analysis of independent-sample t tests.Results:Petasin significantly inhibited the proliferation of human colon carcinoma cell lines,induced apoptosis,and suppressed migration and invasion in SW-620 cells.Western blotting results showed that petasin decreased the phosphorylation of Akt(1.01±0.16 vs.0.74±0.06,P=0.042),mTOR(0.71±0.12 vs.0.32±0.11,P=0.013),and P70S6K(1.23±0.21 vs.0.85±0.14,P=0.008),elevated the expression of caspase-3(0.41±0.09 vs.0.74±0.12,P=0.018)and caspase-9(1.10±0.27 vs.1.98±0.22,P=0.009),decreased the Bcl-2 protein(2.75±0.47 vs.1.51±0.36,P=0.008),downregulated the expression of matrix metalloproteinase(MMP)-3(1.51±0.31 vs.0.82±0.11,P=0.021)and MMP-9(1.56±0.32 vs.0.94±0.15,P=0.039)in SW-620 cell.In vivo,10 mg/kg petasin inhibited tumor growth in Balb/c nude mice(924.18±101.23 vs.577.67±75.12 mm3 at day 28,P=0.001)and induced apoptosis(3.6±0.7%vs.36.0±4.9%,P=0.001)in tumor tissues.Conclusions:Petasin inhibits the proliferation of colon cancer SW-620 cells via inactivating the Akt/mTOR pathway.Our findings suggest petasin as a potential candidate for colon cancer therapy.展开更多
Background:Endothelial dysfunction,the initial pathogenic factor in atherosclerosis,can be alleviated via transient limb ischemia.We observed the effects of regular transient limb ischemia(RTLI)on atherosclerosis in h...Background:Endothelial dysfunction,the initial pathogenic factor in atherosclerosis,can be alleviated via transient limb ischemia.We observed the effects of regular transient limb ischemia(RTLI)on atherosclerosis in hypercholesterolemic rabbits.Methods:Twenty-eight rabbits were randomized to control,cholesterol,sham,ischemia groups(n=7 each)between October 2010 and March 2011.They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks.Six cycles of RTLI were performed once per day on the ischemia group.Serum samples were prepared to measure the total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)before the experiment(W0),at the end of weeks 4,8,12(W4,W8,W12).The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque.The plaque area was measured using Image J.Results were analyzed by analysis of variance or rank sum test.Results:Concentrations of TC in the cholesterol group were higher than those in the control group at W4(29.60[23.75,39.30]vs.1.00[0.80,1.55],Z=–2.745,P=0.006),W8(41.78[28.08,47.37]vs.0.35[0.10,0.68],Z=–2.739,P=0.006),W12(48.32[40.04,48.95]vs.0.61[0.50,0.86],Z=–2.739,P=0.006).Similar results were obtained for HDL-C and LDL-C.Serum concentrations of TC,HDL-C,and LDL-C in the hypercholesterolemic groups had no differences(all P>0.05).The percentage of plaque area in the cholesterol group was higher than that in the control group(47.22±23.89%vs.0,Z=–2.986,P=0.003).Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol(0.44±0.13 vs.0.67±0.18,P=0.014)or sham groups(0.44±0.13 vs.0.61±0.12,P=0.049).Conclusion:In hypercholesterolemic rabbits,RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.展开更多
文摘Petasin is a potential antitumor against human neuroblastoma cell SK-N-SH by inhibiting the ERK1/2 phosphorylation. In view of its great activity and new antiproliferative mechanisms, a series of petasin derivatives were designed and synthesized, which showed great antiproliferative activity. Among them compounds 1h and 1f were more effective against SK-N-SH cells than petasin with the IC50 values of 0.87 and 2.63 μM, respectively.
文摘Background:Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far.Petasin,a natural product found in plants of the genus Petasites,has been reported to possess anticancer activity.The present study aimed to investigate the anticolon cancer activity of petasin both in vitro and in vivo.The molecular mechanism of petasin was also further explored.Methods:Caco-2,LoVo,SW-620,and HT-29 cell lines were used to detect the inhibitory effect of petasin on colon cancer proliferation.Cell viability was determined using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide)assay.Cell apoptosis was analyzed by flow cytometry.Hoechst 33258 staining was used to visualize morphological changes.Cell migration was assessed using a wound-healing migration assay,and cell invasion was investigated using Transwell chambers.Western blotting assays were employed to evaluate the expression levels of proteins in the protein kinase B/mammalian target of rapamycin(Akt/mTOR)signaling pathway.Finally,in vivo activity of petasin was evaluated using the SW-620 subcutaneous tumor model established in Balb/c nude mice.Twelve rats were randomly divided into control group and 10 mg/kg petasin group.The tumor volume was calculated every 7 days for 28 days.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay was performed to assess the apoptotic effect of petasin.Differences between two groups were assessed by analysis of independent-sample t tests.Results:Petasin significantly inhibited the proliferation of human colon carcinoma cell lines,induced apoptosis,and suppressed migration and invasion in SW-620 cells.Western blotting results showed that petasin decreased the phosphorylation of Akt(1.01±0.16 vs.0.74±0.06,P=0.042),mTOR(0.71±0.12 vs.0.32±0.11,P=0.013),and P70S6K(1.23±0.21 vs.0.85±0.14,P=0.008),elevated the expression of caspase-3(0.41±0.09 vs.0.74±0.12,P=0.018)and caspase-9(1.10±0.27 vs.1.98±0.22,P=0.009),decreased the Bcl-2 protein(2.75±0.47 vs.1.51±0.36,P=0.008),downregulated the expression of matrix metalloproteinase(MMP)-3(1.51±0.31 vs.0.82±0.11,P=0.021)and MMP-9(1.56±0.32 vs.0.94±0.15,P=0.039)in SW-620 cell.In vivo,10 mg/kg petasin inhibited tumor growth in Balb/c nude mice(924.18±101.23 vs.577.67±75.12 mm3 at day 28,P=0.001)and induced apoptosis(3.6±0.7%vs.36.0±4.9%,P=0.001)in tumor tissues.Conclusions:Petasin inhibits the proliferation of colon cancer SW-620 cells via inactivating the Akt/mTOR pathway.Our findings suggest petasin as a potential candidate for colon cancer therapy.
基金grants from the Science and Technology Project(No.2011B080701029)Natural Science Foundation(No.2016A030313303)from the Department of Science and Technology of Guangdong province.
文摘Background:Endothelial dysfunction,the initial pathogenic factor in atherosclerosis,can be alleviated via transient limb ischemia.We observed the effects of regular transient limb ischemia(RTLI)on atherosclerosis in hypercholesterolemic rabbits.Methods:Twenty-eight rabbits were randomized to control,cholesterol,sham,ischemia groups(n=7 each)between October 2010 and March 2011.They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks.Six cycles of RTLI were performed once per day on the ischemia group.Serum samples were prepared to measure the total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)before the experiment(W0),at the end of weeks 4,8,12(W4,W8,W12).The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque.The plaque area was measured using Image J.Results were analyzed by analysis of variance or rank sum test.Results:Concentrations of TC in the cholesterol group were higher than those in the control group at W4(29.60[23.75,39.30]vs.1.00[0.80,1.55],Z=–2.745,P=0.006),W8(41.78[28.08,47.37]vs.0.35[0.10,0.68],Z=–2.739,P=0.006),W12(48.32[40.04,48.95]vs.0.61[0.50,0.86],Z=–2.739,P=0.006).Similar results were obtained for HDL-C and LDL-C.Serum concentrations of TC,HDL-C,and LDL-C in the hypercholesterolemic groups had no differences(all P>0.05).The percentage of plaque area in the cholesterol group was higher than that in the control group(47.22±23.89%vs.0,Z=–2.986,P=0.003).Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol(0.44±0.13 vs.0.67±0.18,P=0.014)or sham groups(0.44±0.13 vs.0.61±0.12,P=0.049).Conclusion:In hypercholesterolemic rabbits,RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
