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- Title
Citrus limon L.-Derived Nanovesicles Show an Inhibitory Effect on Cell Growth in p53-Inactivated Colorectal Cancer Cells via the Macropinocytosis Pathway.
- Authors
Takakura, Hideki; Nakao, Toshimasa; Narita, Takumi; Horinaka, Mano; Nakao-Ise, Yukako; Yamamoto, Tetsushi; Iizumi, Yosuke; Watanabe, Motoki; Sowa, Yoshihiro; Oda, Keisuke; Mori, Nobuhiro; Sakai, Toshiyuki; Mutoh, Michihiro
- Abstract
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.
- Subjects
LEMON; PINOCYTOSIS; COLORECTAL cancer; CELL growth; CANCER cells; ULTRACENTRIFUGATION
- Publication
Biomedicines, 2022, Vol 10, Issue 6, p1352
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines10061352