An extract from ripe fruit of Vitex agnus-castus (Vitex) has been used to treat patients with various obstetric and gynecological disorders in Europe. We have demonstrated that Vitex showed cytocidal effects on variou...An extract from ripe fruit of Vitex agnus-castus (Vitex) has been used to treat patients with various obstetric and gynecological disorders in Europe. We have demonstrated that Vitex showed cytocidal effects on various types of cancer cell lines including a human colon carcinoma cell line, COLO 201. In this study, we extended our previous study to investigate the detailed mechanisms underlying cytocidal effects of Vi- tex on COLO 201. Furthermore, a possible clinical application of Vitex was also explored in vivo using nude mice xenografted with the cells. Treatment with Vitex induced apoptosis in COLO 201 in a time-dependent manner, accompanying with activa-tion of caspase-9 and -3, but not caspase-8. An inhibitor for c-Jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK), significantly suppressed the apoptosis induction along with caspase-3 activation. Endoplasmic reticulum (ER) stress-related genes were also upregulated by Vitex treatment. Most importantly, the in vivo efficacy of Vitex evaluated by assessing the tumor growth revealed that the administration of Vitex significantly suppressed tumor growth in COLO 201 xenografted mice. Collectively, current results suggest that apoptosis induction by Vitex in COLO 201 is mediated through the activation of JNK and caspase-9, -3 resulted from ER stress. Based on the current clinical application of Vitex, these results thus provide a new insight into the clinical use of Vitex and leave open a possibility of a new regimen as an alternative medicine approach for such devastating colon cancer treatment.展开更多
The method to increase PtRu utilization and its catalytic activity of PtRu nanoparticles supported on reduced graphene oxide(RGO)by avoiding its restacking was proposed with the aim of developing an active catalyst fo...The method to increase PtRu utilization and its catalytic activity of PtRu nanoparticles supported on reduced graphene oxide(RGO)by avoiding its restacking was proposed with the aim of developing an active catalyst for a direct methanol fuel cell.The heat treatment at 200◦C of the GO aerogel(GOA)prepared by freeze drying of GO ice was introduced to weaken the attractive force of the hydrogen bonding between the GO sheets followed by the composite with the nanoparticles,i.e.,ketjenblack(KB),TiO_(2)and Ti_(4)O_(7),at different weight ratios.The catalyst supported on the heat-treated GOA(RGOA),PtRu/RGOA,improved the PtRu utilization to some extent and also increased the ECSA and mass activity compared to that of PtRu/RGO.RGOA had fewer oxygen functional groups,especially the epoxy groups.Due to the treatment and composite,the PtRu utilization was increased from 66.5%for PtRu/RGO to 128.6%for PtRu/RGOA+Ti_(4)O_(7)(4:1)and the mass activity was improved from 50.7 A/g-PtRu for PtRu/RGO to 130.5 A/g-PtRu for PtRu/RGOA+Ti_(4)O_(7)(1:1).The Ti_(4)O_(7)nanoparticles showed the best catalytic performance for the composite suggesting that the strong interaction between Ti_(4)O_(7)and the Pt nanoparticles was effective due to its high electronic conductivity.展开更多
文摘An extract from ripe fruit of Vitex agnus-castus (Vitex) has been used to treat patients with various obstetric and gynecological disorders in Europe. We have demonstrated that Vitex showed cytocidal effects on various types of cancer cell lines including a human colon carcinoma cell line, COLO 201. In this study, we extended our previous study to investigate the detailed mechanisms underlying cytocidal effects of Vi- tex on COLO 201. Furthermore, a possible clinical application of Vitex was also explored in vivo using nude mice xenografted with the cells. Treatment with Vitex induced apoptosis in COLO 201 in a time-dependent manner, accompanying with activa-tion of caspase-9 and -3, but not caspase-8. An inhibitor for c-Jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK), significantly suppressed the apoptosis induction along with caspase-3 activation. Endoplasmic reticulum (ER) stress-related genes were also upregulated by Vitex treatment. Most importantly, the in vivo efficacy of Vitex evaluated by assessing the tumor growth revealed that the administration of Vitex significantly suppressed tumor growth in COLO 201 xenografted mice. Collectively, current results suggest that apoptosis induction by Vitex in COLO 201 is mediated through the activation of JNK and caspase-9, -3 resulted from ER stress. Based on the current clinical application of Vitex, these results thus provide a new insight into the clinical use of Vitex and leave open a possibility of a new regimen as an alternative medicine approach for such devastating colon cancer treatment.
基金supported by JSPS KAKENHI Grant Number JP18H01772 and 21H01698.
文摘The method to increase PtRu utilization and its catalytic activity of PtRu nanoparticles supported on reduced graphene oxide(RGO)by avoiding its restacking was proposed with the aim of developing an active catalyst for a direct methanol fuel cell.The heat treatment at 200◦C of the GO aerogel(GOA)prepared by freeze drying of GO ice was introduced to weaken the attractive force of the hydrogen bonding between the GO sheets followed by the composite with the nanoparticles,i.e.,ketjenblack(KB),TiO_(2)and Ti_(4)O_(7),at different weight ratios.The catalyst supported on the heat-treated GOA(RGOA),PtRu/RGOA,improved the PtRu utilization to some extent and also increased the ECSA and mass activity compared to that of PtRu/RGO.RGOA had fewer oxygen functional groups,especially the epoxy groups.Due to the treatment and composite,the PtRu utilization was increased from 66.5%for PtRu/RGO to 128.6%for PtRu/RGOA+Ti_(4)O_(7)(4:1)and the mass activity was improved from 50.7 A/g-PtRu for PtRu/RGO to 130.5 A/g-PtRu for PtRu/RGOA+Ti_(4)O_(7)(1:1).The Ti_(4)O_(7)nanoparticles showed the best catalytic performance for the composite suggesting that the strong interaction between Ti_(4)O_(7)and the Pt nanoparticles was effective due to its high electronic conductivity.