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Citrus limonL.-Derived Nanovesicles Show an Inhibitory Effect on Cell Growth in p53-Inactivated Colorectal Cancer
Hideki Takakura1,2,3, Toshimasa Nakao1, Takumi Narita1
1Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
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.
Insights
Edible nanovesicles from lemons show promise for preventing colorectal cancer (CRC). These nanovesicles are taken up by CRC cells via macropinocytosis, inhibiting growth regardless of p53 gene status.
Area of Science:
- Plant-derived nanovesicles
- Cancer research
- Cellular biology
Background:
- Colorectal cancer (CRC) affects approximately 70% of patients with a p53 mutation, indicating a poor prognosis.
- The role of p53 inactivation in activating the macropinocytosis pathway for CRC prevention remains unclear.
- Plant-derived nanovesicles are being investigated for their potential in CRC prevention.
Purpose of the Study:
- To investigate the effect of Citrus limon L.-derived nanovesicles on p53-wild and p53-inactivated colorectal cancer (CRC) cells.
- To determine if p53 inactivation activates the macropinocytosis pathway.
- To elucidate the mechanism of CRC cell growth inhibition by Citrus limon L.-derived nanovesicles.
Main Methods:
- Isolation of Citrus limon L.-derived nanovesicles using ultracentrifugation.
- Treatment of p53-wild and p53-null CRC cells with Citrus limon L.-derived nanovesicles.
- Analysis of nanovesicle uptake via the macropinocytosis pathway.
Main Results:
- Citrus limon L.-derived nanovesicles exhibited inhibitory effects on both p53-wild and p53-inactivated CRC cells.
- P53 inactivation was found to activate the macropinocytosis pathway.
- Citrus limon L.-derived nanovesicles were internalized through macropinocytosis, independent of citrate's inhibitory effects.
Conclusions:
- A novel mechanism involving macropinocytosis-mediated growth inhibition by Citrus limon L.-derived nanovesicles in CRC cells was identified.
- These findings suggest the potential development of functional food products containing Citrus limon L.-derived nanovesicles for preventing p53-inactivation CRC.
- The study highlights the therapeutic potential of plant-derived nanovesicles in cancer prevention.
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