OBJECTIVE Ascorbic acid(AA),commonly known as vitamin C,is a small molecular widely distributed in in food and traditional herbs.Recently,there are some literatures reported that high concentration AA could selectivel...OBJECTIVE Ascorbic acid(AA),commonly known as vitamin C,is a small molecular widely distributed in in food and traditional herbs.Recently,there are some literatures reported that high concentration AA could selectively kill the cancer cells but not the normal cells.This study was designed to explore the underlying mechanisms.METHODS Colorectal cancer line cells were cultured and treated with AA.The cytotoxic,intracellular ATP level,reactive oxygen species,calcium,were determined with commercial kits and fluorescent probes.RESULTS High concentration of AA induced cell death in HCT116 and HT29 colorectal cancer cells in concentration-and time-dependent manner.AA treat⁃ment induced ATP decrease,LDH release,cell swollen and loss of plasma membrane integrity.Pharmacological inhibi⁃tors for apoptosis,necroptosis,autophagy,pyroptosis and oncosis showed no effect on AA-induced cell death.Further⁃more,ROS level increase and intracellular calcium(Ca2+)accumulation were observed after AA treatment.ROS scavenger N-acetyl cysteine(NAC),intracellular calcium chelator BAPTA-AM and intracellular calcium inhibitor 2-aminoethoxy⁃diphenyl borate(2-APB)could attenuate the cell death induced by AA.NAC could attenuate both ROS increase and intracellular Ca2+accumulation induced by AA,while BAPTA-AM could only attenuate intracellular Ca2+accumulation.In addition,high concentration AA induced mitochondrial damage and mitochondrial ROS generation.CONCLUSION AA induces Ca2+-dependent programed necrosis mediated by ROS.Our study provided new insights into high concentration AA induced cell death in human colon cancer cells.展开更多
Cisplatin （CP） , a highly effective and widely used chemotherapeutic agent, has a major limitation for its nephrotoxicity. We recently identified a novel strategy for attenuating its nephrotoxicity in chemotherapy b...Cisplatin （CP） , a highly effective and widely used chemotherapeutic agent, has a major limitation for its nephrotoxicity. We recently identified a novel strategy for attenuating its nephrotoxicity in chemotherapy by an ef- fective adjuvant via epigenetic modification through targeting Histone deacetylase 2 （HDAC2）. Glycyrrhizic acid （GA） ,a major active component of Licorice, was described here for its new application. Molecular docking and Surface Plasmon resonance （SPR） assay firstly reported that 18βGA, GA metabolite in vivo, could directly bind to HDAC2 and prevent HDAC2 activation. The effects and mechanisms of GA and its major metabolite 18βGA were assessed in CP-induced acute kidney injury （AKI） in C57BL/6 mice, and in CP-treated HK-2 and mTEC cells lines. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） and flow cytometry （FCM） results confirmed that GA and 18βGA could inhibit apoptosis of renal tubular epithelial cells induced by CP in vivo and in vitro. Western blot and immunofluorescence results demonstrated that the expression of bone morphogenetic protein- 7 （BMP-7） , a protective molecule in renal inflammation, was clearly induced by 18βGA in AKI models while siR- NA BMP-7 could reduce the inhibitory effect of 18βGA on apoptosis. Results of current study indicated that 18βGA inhibited apoptosis of renal tubular epithelial cells via enhancing level of BMP-7 epigenetically through targeting HDAC2, therefore protecting against CP-induced AKI. These available evidence, which led to an improved under- standing of molecular recognition, suggested that 18βGA could serve as a potential clinical adjuvant in chemothera-展开更多
利用线性电位扫描、恒电位阶跃、交流阻抗等方法分别研究了Pb Ca Bi合金被阳极或阴极极化后,表面上析氧、析氢以及合金腐蚀行为。结果表明:与Pb Ca合金相比,Pb Ca Bi合金可增加氧的析出,但抑制氢的析出,同时铋的加入,使Pb Ca耐蚀性提高...利用线性电位扫描、恒电位阶跃、交流阻抗等方法分别研究了Pb Ca Bi合金被阳极或阴极极化后,表面上析氧、析氢以及合金腐蚀行为。结果表明:与Pb Ca合金相比,Pb Ca Bi合金可增加氧的析出,但抑制氢的析出,同时铋的加入,使Pb Ca耐蚀性提高,且不同含量的铋对合金腐蚀有不同的影响。展开更多
基金Science and Technology Development Fund,Macao SAR(078/2016/A2)Research Fund of University of Macao(MYRG2016-00043-ICMS-QRCM)
文摘OBJECTIVE Ascorbic acid(AA),commonly known as vitamin C,is a small molecular widely distributed in in food and traditional herbs.Recently,there are some literatures reported that high concentration AA could selectively kill the cancer cells but not the normal cells.This study was designed to explore the underlying mechanisms.METHODS Colorectal cancer line cells were cultured and treated with AA.The cytotoxic,intracellular ATP level,reactive oxygen species,calcium,were determined with commercial kits and fluorescent probes.RESULTS High concentration of AA induced cell death in HCT116 and HT29 colorectal cancer cells in concentration-and time-dependent manner.AA treat⁃ment induced ATP decrease,LDH release,cell swollen and loss of plasma membrane integrity.Pharmacological inhibi⁃tors for apoptosis,necroptosis,autophagy,pyroptosis and oncosis showed no effect on AA-induced cell death.Further⁃more,ROS level increase and intracellular calcium(Ca2+)accumulation were observed after AA treatment.ROS scavenger N-acetyl cysteine(NAC),intracellular calcium chelator BAPTA-AM and intracellular calcium inhibitor 2-aminoethoxy⁃diphenyl borate(2-APB)could attenuate the cell death induced by AA.NAC could attenuate both ROS increase and intracellular Ca2+accumulation induced by AA,while BAPTA-AM could only attenuate intracellular Ca2+accumulation.In addition,high concentration AA induced mitochondrial damage and mitochondrial ROS generation.CONCLUSION AA induces Ca2+-dependent programed necrosis mediated by ROS.Our study provided new insights into high concentration AA induced cell death in human colon cancer cells.
文摘Cisplatin （CP） , a highly effective and widely used chemotherapeutic agent, has a major limitation for its nephrotoxicity. We recently identified a novel strategy for attenuating its nephrotoxicity in chemotherapy by an ef- fective adjuvant via epigenetic modification through targeting Histone deacetylase 2 （HDAC2）. Glycyrrhizic acid （GA） ,a major active component of Licorice, was described here for its new application. Molecular docking and Surface Plasmon resonance （SPR） assay firstly reported that 18βGA, GA metabolite in vivo, could directly bind to HDAC2 and prevent HDAC2 activation. The effects and mechanisms of GA and its major metabolite 18βGA were assessed in CP-induced acute kidney injury （AKI） in C57BL/6 mice, and in CP-treated HK-2 and mTEC cells lines. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） and flow cytometry （FCM） results confirmed that GA and 18βGA could inhibit apoptosis of renal tubular epithelial cells induced by CP in vivo and in vitro. Western blot and immunofluorescence results demonstrated that the expression of bone morphogenetic protein- 7 （BMP-7） , a protective molecule in renal inflammation, was clearly induced by 18βGA in AKI models while siR- NA BMP-7 could reduce the inhibitory effect of 18βGA on apoptosis. Results of current study indicated that 18βGA inhibited apoptosis of renal tubular epithelial cells via enhancing level of BMP-7 epigenetically through targeting HDAC2, therefore protecting against CP-induced AKI. These available evidence, which led to an improved under- standing of molecular recognition, suggested that 18βGA could serve as a potential clinical adjuvant in chemothera-
