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2-(3-Be nzoylth iou reido)-4,5,6,7-tet ra hydro be n zo [b ] thiophene-3-carboxylic acid ameliorates metabolic disorders in high-fat diet-fed mice
  • ISSN号:1671-4083
  • 期刊名称:《中国药理学报:英文版》
  • 分类:Q55[生物学—生物化学] Q279[生物学—细胞生物学]
  • 作者机构:[1]National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, ChineseAcademy of Sciences, Shanghai 201203, China
  • 相关基金:This work was supported by grants from the National Natu- ral Science Foundation of China (No 81473244, 81270942, and 81125023), and the National Science and Technology Major Projects for “Major New Drugs Innovation and Development” (2012ZX09301001-004, 2013ZX09508104).
中文摘要:

目的: 在 vitro 和它的 anticancer 机制在人的结肠癌房间上从 Physalis divericata 曝晒调查 physalin B 的效果。

英文摘要:

Aim: To investigate the effects of physalin B insolated from Physalis divericata on human colon cancer cells in vitro and its anticancer mechanisms. Methods: Human HCT116 colon cancer cell line was tested. Cell viability and apoptosis were detected, and relevant proteins were measured using Western blot analyses. Autophagosomes were observed in stable GFP-LC3 HCT116 cells. Localization of autophagosomes and lysosomes was evaluated in GFP-LC3/RFP-LAMPl-co-transfected cells. Microtubules and F-actin microfilaments were observed with confocal microscope. Mitochondrial ROS (mito-ROS) was detected with flow cytometry in the cells stained with MitoSox dye. Results: Physalin B inhibited the viability of HCT116 cells with an IC_50 value of 1.35 pmol/L. Treatment of the cells with physalin B (2.5-10 μmol/L) induced apoptosis and the cleavage of PARP and caspase-3. Meanwhile, physalin B treatment induced autophagosome formation, and accumulation of LC3-11 and p62, but decreased Beclin I protein level. Marked changes of microtubules and F-actin microfilaments were observed in physalin B-treated cells, which led to the blockage of co-localization of autophagosomes and lysosomes. Physalin B treatment dose-dependently increased the phosphorylation of p38, ERK and JNK in the cells, whereas the p38 inhibitor SB202190, ERK inhibitor U0126 or JNK inhibitor SP600125 could partially reduce physalin B-induced PARP cleavage and p62 accumulation. Moreover, physalin B treatment dose-dependently increased mito-ROS production in the cells, whereas the ROS scavenger NAC could reverse physalin B-induced effects, including incomplete autophagic response, accumulation of ubiquitinated proteins, changes of microtubules and F-actin, activation of p38, ERK and JNK, as well as cell death and apoptosis. Conclusion: Physalin B induces mito-ROS, which not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in HCT116 cells in vitro.

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期刊信息
  • 《中国药理学报:英文版》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中科院上海药物研究所
  • 主编:丁光生
  • 地址:上海市太原路294号31号楼
  • 邮编:200031
  • 邮箱:
  • 电话:021-54922821 54922822
  • 国际标准刊号:ISSN:1671-4083
  • 国内统一刊号:ISSN:31-1347/R
  • 邮发代号:4-295
  • 获奖情况:
  • 1992、1996年两届全国优秀科技期刊一等奖,1992、1996、1997年中国科协、中科院以及上海市优...,首届国家期刊奖、2000年中科院优秀期刊评比特别奖
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  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,美国剑桥科学文摘,美国科学引文索引(扩展库),美国生物科学数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,英国食品科技文摘,中国北大核心期刊(2000版)
  • 被引量:1239