AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(a human colo...AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce Lo Vo cancer cell growth. Cyclooxygenase 2(COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2(PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control.RESULTS Our results showed that 20 μmol/L TQ significantly reduced human LoV o colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3 K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoV o cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoV o cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSION TQ inhibits LoV o cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.展开更多
To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, se...To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.展开更多
AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection an...AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM(Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, Lo Vo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT(Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber(Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator(u-PA), tissue-type plasminogen activator(t-PA) and matrix metalloproteinase(MMP)-9 in human Lo Vo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test.RESULTS: The structure was first compared with E2 and ER agonists. We then treated the Lo Vo cells with E2 and ER agonists(10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human Lo Vo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17β-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human Lo Vo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17β-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17β-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in Lo Vo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on Lo Vo cells. That E2 and/or ER agonists may impair Lo Vo cell migration by modulating migration-related factors via the p53 tumor suppressor gene.CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future.展开更多
基金Supported by (in part) the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence,No.MOHW105-TDU-B-212-133019
文摘AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce Lo Vo cancer cell growth. Cyclooxygenase 2(COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2(PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control.RESULTS Our results showed that 20 μmol/L TQ significantly reduced human LoV o colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3 K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoV o cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoV o cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSION TQ inhibits LoV o cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.
基金Supported by Grants from the National Science Council,Far Eastern Medical FoundationTzu Chi Charitable Foundation
文摘To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.
基金Supported by Taiwan Department of Health Clinical Trial and Re-search Center of Excellence No.MOHW103-TDU-B-212-113002
文摘AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM(Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, Lo Vo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT(Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber(Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator(u-PA), tissue-type plasminogen activator(t-PA) and matrix metalloproteinase(MMP)-9 in human Lo Vo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test.RESULTS: The structure was first compared with E2 and ER agonists. We then treated the Lo Vo cells with E2 and ER agonists(10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human Lo Vo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17β-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human Lo Vo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17β-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17β-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in Lo Vo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on Lo Vo cells. That E2 and/or ER agonists may impair Lo Vo cell migration by modulating migration-related factors via the p53 tumor suppressor gene.CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future.