Carica papaya L. Hexane Fraction Induces Apoptotic Cell Death in Colorectal Cancer Cells via PI3K/AKT Suppression and Impaired Late-Stage Autophagic Flux
5 affiliations
- 1Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Republic of Korea
- 2Graduate Program for Bio-Health/Innovative Drug Development Using Subtropical Bio-Resources, Jeju National University, Jeju 63243, Republic of Korea
- 3Bio-Health Materials Core-Facility Center, Jeju National University, Jeju 63243, Republic of Korea
- 4Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Republic of Korea
- 5Research Institute of Climate Change and Agriculture, National Institute of Horticultural and Herbal Science, Rural Development Administration, Jeju 63243, Republic of Korea
Abstract
Background/Objectives: Colorectal cancer (CRC) remains a major contributor to cancer-associated deaths globally. Carica papaya L., a tropical fruit species, is reported to contain a wide range of biological properties, along with potential anticancer effects. However, studies evaluating the therapeutic potential and molecular mechanisms of Korean Carica papaya L. cultivars against CRC are limited. Therefore, this study investigated the effect of the hexane fraction of Carica papaya L. on the induction of apoptosis and the underlying mechanisms associated with this effect in human CRC cells. Methods: We performed several in vitro experiments, including cell viability, apoptosis, assessment of autophagic vacuoles, Western blotting, and analysis of autophagic flux. Subsequently, we verified the findings in an animal model of CRC induced by azoxymethane/dextran sulfate sodium. Results: BR 56 Hex F reduced cell viability and induced caspase-7/9-dependent apoptosis accompanied by intracellular and mitochondrial reactive oxygen species elevation. Mechanistically, BR 56 Hex F suppressed phosphatidylinositol 3-kinase (PI3K; p85/p110), p-AKT (Ser473/Thr308), and mammalian target of rapamycin signaling. Although autophagosome formation was initiated, the late-stage autophagic flux was impaired, as evidenced by p62 accumulation, LAMP-1 depletion, and autophagosome accumulation. In vivo, oral administration of BR 56 C. papaya L. extract significantly attenuated azoxymethane/dextran sulfate sodium-induced colon shortening, splenomegaly, histopathological damage, and colonic PI3K and p-AKT expression. Conclusions: BR 56 Hex F inhibited CRC growth by suppressing PI3K/AKT signaling and impairing late-stage autophagic flux, representing a potential natural candidate for CRC treatment.
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BibTeX
@article{perera2026carica,
title = {{Carica papaya L. Hexane Fraction Induces Apoptotic Cell Death in Colorectal Cancer Cells via PI3K/AKT Suppression and Impaired Late-Stage Autophagic Flux}},
author = {Rambukkana Maggonage Thiruni Dananjana Perera and Su-Lim Kim and Ji-Hyang Kim and Kyeoung Cheol Kim and Kang-Ui Tak and Seung Min Lee and Chankyu Lim and Dong-Sun Lee},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213557},
url = {https://www.mdpi.com/2072-6643/18/21/3557},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Carica papaya L. Hexane Fraction Induces Apoptotic Cell Death in Colorectal Cancer Cells via PI3K/AKT Suppression and Impaired Late-Stage Autophagic Flux
AU - Rambukkana Maggonage Thiruni Dananjana Perera
AU - Su-Lim Kim
AU - Ji-Hyang Kim
AU - Kyeoung Cheol Kim
AU - Kang-Ui Tak
AU - Seung Min Lee
AU - Chankyu Lim
AU - Dong-Sun Lee
PY - 2026
DA - 2026/10/28
JO - Nutrients
DO - 10.3390/nu18213557
UR - https://www.mdpi.com/2072-6643/18/21/3557
AB - Background/Objectives: Colorectal cancer (CRC) remains a major contributor to cancer-associated deaths globally. Carica papaya L., a tropical fruit species, is reported to contain a wide range of biological properties, along with potential anticancer effects. However, studies evaluating the therapeutic potential and molecular mechanisms of Korean Carica papaya L. cultivars against CRC are limited. Therefore, this study investigated the effect of the hexane fraction of Carica papaya L. on the induction of apoptosis and the underlying mechanisms associated with this effect in human CRC cells. Methods: We performed several in vitro experiments, including cell viability, apoptosis, assessment of autophagic vacuoles, Western blotting, and analysis of autophagic flux. Subsequently, we verified the findings in an animal model of CRC induced by azoxymethane/dextran sulfate sodium. Results: BR 56 Hex F reduced cell viability and induced caspase-7/9-dependent apoptosis accompanied by intracellular and mitochondrial reactive oxygen species elevation. Mechanistically, BR 56 Hex F suppressed phosphatidylinositol 3-kinase (PI3K; p85/p110), p-AKT (Ser473/Thr308), and mammalian target of rapamycin signaling. Although autophagosome formation was initiated, the late-stage autophagic flux was impaired, as evidenced by p62 accumulation, LAMP-1 depletion, and autophagosome accumulation. In vivo, oral administration of BR 56 C. papaya L. extract significantly attenuated azoxymethane/dextran sulfate sodium-induced colon shortening, splenomegaly, histopathological damage, and colonic PI3K and p-AKT expression. Conclusions: BR 56 Hex F inhibited CRC growth by suppressing PI3K/AKT signaling and impairing late-stage autophagic flux, representing a potential natural candidate for CRC treatment.
SN - 2072-6643
ER -