胞饮病
生物
碳酸钙-2
野生型
细胞生物学
突变体
癌症研究
化学
细胞
内吞作用
生物化学
基因
作者
Hideki Takakura,Toshimasa Nakao,Takumi Narita,Mano Horinaka,Yukako Nakao-Ise,Tetsushi Yamamoto,Yosuke Iizumi,Motoki Watanabe,Yoshihiro Sowa,Keisuke Oda,Nobuhiro Mori,Toshiyuki Sakai,Michihiro Mutoh
出处
期刊:Biomedicines
[Multidisciplinary Digital Publishing Institute]
日期:2022-06-08
卷期号:10 (6): 1352-1352
被引量:28
标识
DOI:10.3390/biomedicines10061352
摘要
Edible plant-derived nanovesicles have been explored as effective materials for preventing colorectal cancer (CRC) incidence, dependent on gene status, as a K-Ras-activating mutation via the macropinocytosis pathway. Approximately 70% of CRC harbors the p53 mutation, which is strongly associated with a poor prognosis for CRC. However, it has not been revealed whether p53 inactivation activates the macropinocytosis pathway or not. In this study, we investigated parental cells, wild-type or null for p53 treated with Citrus limon L.-derived nanovesicles, as potential materials for CRC prevention. Using ultracentrifugation, we obtained C. limon L.-derived nanovesicles, the diameters of which were approximately 100 nm, similar to that of the exosomes derived from mammalian cells. C. limon L.-derived nanovesicles showed inhibitory effects on cell growth in not p53-wild, but also in p53-inactivated CRC cells. Furthermore, we revealed that the macropinocytosis pathway is activated by p53 inactivation and C. limon L.-derived nanovesicles were up taken via the macropinocytosis pathway. Notably, although C. limon L.-derived nanovesicles contained citrate, the inhibitory effects of citrate were not dependent on the p53 status. We thus provide a novel mechanism for the growth inhibition of C. limon L.-derived nanovesicles via macropinocytosis and expect to develop a functional food product containing them for preventing p53-inactivation CRC incidence.
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