Background Parthenolide has been tested for anti-tumor activities, such as anti-proliferation and pro-apoptosis in recent studies. However, little is known about its role in the process of tumor angiogenesis. This stu...Background Parthenolide has been tested for anti-tumor activities, such as anti-proliferation and pro-apoptosis in recent studies. However, little is known about its role in the process of tumor angiogenesis. This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation, migration and lumen formation capacity of human umbilical vein endothelial cells. Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells. After 24-hour incubation, the culture supernatants were harvested and used to treat human umbilical vein endothelial cells for 24 hours. Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells. The secretion of vascular endothelial growth factor （VEGF）, interleukin （IL）-8 and matrix metalloproteinases （MMP）-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay （ELISA） assays. Results Suppression of proliferation, migration, and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide. Parthenolide decreased the levels of the angiogenic factors MMP-9, VEGF, and IL-8 secreted by the MDA-MB-231 cells. Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation, migration and lumen-like structure formation of endothelial cells, thereby inhibiting tumor growth. It is a promising potential anti-angiogenic drug.展开更多
The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal ...The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial （HLE） cells and the possible molecular mechanisms involved. HLE cells （SRA01-04） were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide （10, 20 and 50 μM）. To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H202 for 18 h, a high fraction of riLE cells underwent apoptosis, while in the presence ofparthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H202 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation ofcaspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation ofcaspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.展开更多
This study examined the mechanism of the inhibitory effect of parthenolide（PTL） on the activity of NF-κB in multiple myeloma（MM）. Human multiple myeloma cell line RPMI 8226 cells were treated with or without diff...This study examined the mechanism of the inhibitory effect of parthenolide（PTL） on the activity of NF-κB in multiple myeloma（MM）. Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6（TRAF6） and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.展开更多
Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy;however,the underlying mechanism has not been fiilly elucidated.In this st...Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy;however,the underlying mechanism has not been fiilly elucidated.In this study,we aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules.Methods 8-week-old male db/db mice(n=8),a type 2 diabetic nephropathy model,administered with nuclear factor kappa-B(NF-kB)inhibitor parthenolide(PTN,1 mg/kg)intraperitoneally every other day for 8 weeks,were as the treatment group.Meanwhile,the age-matched male db/m mice(n=S)and db/db mice(n=8)were treated with saline as the control group and type 2 diabetic nephropathy group.When the mice were sacrificed,blood and urine were collected to examine homeostasis model assessment of insulin resistance(HOMA-IR)and urine albumin creatinine ratio,and kidney samples were used to analyze histopathologic changes with periodic acid-Schiff(PAS)staining,NF-kB p65,phosphorylation of AKT(p-AKT),amnionless and cubilin expressions with immunohistochemistry as well as western blot,and the albumin uptake of renal tubules by using immunofluorescence.In addition,HKC cells were divided into the insulin group treated with insulin alone,the TNF-a group treated with insulin and tumor necrosis factor(TNF-a),and the TNF-a+PTN group exposed to PTN,insulin and TNF-a.The levels of albumin uptake and expression levels of NF-kB p65,p-IRS-l/IRS-1,p-AKT/AKT,amnionless and cubilin in HKC cells were measured.Results Compared with the db/db group,the db/db+PTN group demonstrated decreased levels of HOMA-IR(36.83±14.09 vs.31.07+28.05)and urine albumin creatinine ratio(190.3±7.3 vs.143.0±97.6 mg/mmol);however,the differences were not statistically significant(P>0.05).Periodic acid-Schiff staining showed PTN could alleviate the glomerular hypertrophy and reduce the matrix in mesangial areas of db/db mice.The renal expression of NF-kB p65 was increased and p-AKT(s473)decreased in the db/db group展开更多
文摘Background Parthenolide has been tested for anti-tumor activities, such as anti-proliferation and pro-apoptosis in recent studies. However, little is known about its role in the process of tumor angiogenesis. This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation, migration and lumen formation capacity of human umbilical vein endothelial cells. Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells. After 24-hour incubation, the culture supernatants were harvested and used to treat human umbilical vein endothelial cells for 24 hours. Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells. The secretion of vascular endothelial growth factor （VEGF）, interleukin （IL）-8 and matrix metalloproteinases （MMP）-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay （ELISA） assays. Results Suppression of proliferation, migration, and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide. Parthenolide decreased the levels of the angiogenic factors MMP-9, VEGF, and IL-8 secreted by the MDA-MB-231 cells. Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation, migration and lumen-like structure formation of endothelial cells, thereby inhibiting tumor growth. It is a promising potential anti-angiogenic drug.
基金supported by National Natural Science Foundation of China(No.30471538)Traditional Chinese Medicine Foundation of Zhejiang province(No.2005C086).
文摘The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial （HLE） cells and the possible molecular mechanisms involved. HLE cells （SRA01-04） were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide （10, 20 and 50 μM）. To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H202 for 18 h, a high fraction of riLE cells underwent apoptosis, while in the presence ofparthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H202 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation ofcaspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation ofcaspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.
基金supported by the National Natural Science Foundation of China(No.81272624)
文摘This study examined the mechanism of the inhibitory effect of parthenolide（PTL） on the activity of NF-κB in multiple myeloma（MM）. Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6（TRAF6） and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.
基金the Natural Science Foundation of Beijing,China(Grant No.7122143).
文摘Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy;however,the underlying mechanism has not been fiilly elucidated.In this study,we aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules.Methods 8-week-old male db/db mice(n=8),a type 2 diabetic nephropathy model,administered with nuclear factor kappa-B(NF-kB)inhibitor parthenolide(PTN,1 mg/kg)intraperitoneally every other day for 8 weeks,were as the treatment group.Meanwhile,the age-matched male db/m mice(n=S)and db/db mice(n=8)were treated with saline as the control group and type 2 diabetic nephropathy group.When the mice were sacrificed,blood and urine were collected to examine homeostasis model assessment of insulin resistance(HOMA-IR)and urine albumin creatinine ratio,and kidney samples were used to analyze histopathologic changes with periodic acid-Schiff(PAS)staining,NF-kB p65,phosphorylation of AKT(p-AKT),amnionless and cubilin expressions with immunohistochemistry as well as western blot,and the albumin uptake of renal tubules by using immunofluorescence.In addition,HKC cells were divided into the insulin group treated with insulin alone,the TNF-a group treated with insulin and tumor necrosis factor(TNF-a),and the TNF-a+PTN group exposed to PTN,insulin and TNF-a.The levels of albumin uptake and expression levels of NF-kB p65,p-IRS-l/IRS-1,p-AKT/AKT,amnionless and cubilin in HKC cells were measured.Results Compared with the db/db group,the db/db+PTN group demonstrated decreased levels of HOMA-IR(36.83±14.09 vs.31.07+28.05)and urine albumin creatinine ratio(190.3±7.3 vs.143.0±97.6 mg/mmol);however,the differences were not statistically significant(P>0.05).Periodic acid-Schiff staining showed PTN could alleviate the glomerular hypertrophy and reduce the matrix in mesangial areas of db/db mice.The renal expression of NF-kB p65 was increased and p-AKT(s473)decreased in the db/db group
