The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy

The immature fruits of Poncirus trifoliate are used as a medicine for the treatment of gastrointestinal disorders, inflammation, and allergies in East Asia. However, their effect on colon cancer cells remains unclear. We investigated the effect of the immature fruit of P. trifoliate extract on color...

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Main Authors: Sun-Young Kim, Ho-Keun Yi, Bong-Sik Yun, Dae-Yeol Lee, Pyung Han Hwang, Hae-Ryong Park, Min Sun Kim
Format: Article
Language:English
Published: Tsinghua University Press 2020-09-01
Series:Food Science and Human Wellness
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213453020301397
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author Sun-Young Kim
Ho-Keun Yi
Bong-Sik Yun
Dae-Yeol Lee
Pyung Han Hwang
Hae-Ryong Park
Min Sun Kim
author_facet Sun-Young Kim
Ho-Keun Yi
Bong-Sik Yun
Dae-Yeol Lee
Pyung Han Hwang
Hae-Ryong Park
Min Sun Kim
author_sort Sun-Young Kim
collection DOAJ
description The immature fruits of Poncirus trifoliate are used as a medicine for the treatment of gastrointestinal disorders, inflammation, and allergies in East Asia. However, their effect on colon cancer cells remains unclear. We investigated the effect of the immature fruit of P. trifoliate extract on colorectal adenocarcinoma. The extract of the immature fruit of P. trifoliata inhibited the proliferation of CT-26 cells compared with untreated cells and it induced autophagy and apoptosis through the protein kinase B/mammalian target of rapamycin and 5′-AMP-activated protein kinase pathways. The number of autophagic vacuoles and autophage markers increased in response to the extract. At later time-points, apoptosis increased dose/time-dependently. In CT-26 cells pre-treated a pan-caspase inhibitor prior to P. trifoliata immature fruit extract treatment, we did not find any change in pro-caspase 3 and pro-PARP levels. Additionally, in cells pre-treated autphage inhibitor, SQSTM1/p62 and LC3AB, pro-caspase 3 and pro-PARP levels did not change. Our results indicate the molecular mechanisms that the extract of the immature fruit of P. trifoliata induces apoptosis in colorectal carcinoma cells by inducing mitochondrial autophagy. In this study, we provided a draft for further investigate the use of MEPT for colorectal cancer inhibition.
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spelling doaj-art-0b0b3614d2c646f3b1167aebcebf8eb52025-02-03T06:34:59ZengTsinghua University PressFood Science and Human Wellness2213-45302020-09-0193237244The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagySun-Young Kim0Ho-Keun Yi1Bong-Sik Yun2Dae-Yeol Lee3Pyung Han Hwang4Hae-Ryong Park5Min Sun Kim6Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54907, South KoreaDepartment of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University, Jeonju, 54907, South KoreaDivision of Biotechnology and Advanced Institute of Environment and Bioscience, Jeonbuk National University, Iksan-si, 54596, South KoreaResearch Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54907, South Korea; Department of Pediatrics, Jeonbuk National University Medical School, Jeonju, 54907, South KoreaResearch Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54907, South Korea; Department of Pediatrics, Jeonbuk National University Medical School, Jeonju, 54907, South KoreaDepartment of Food Science and Biotechnology, Kyungnam University, Changwon-si, 51767, South KoreaResearch Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54907, South Korea; Department of Pediatrics, Jeonbuk National University Medical School, Jeonju, 54907, South Korea; Corresponding author at: Department of Pediatrics, Jeonbuk National University Hospital, 20 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, 54907, South Korea.The immature fruits of Poncirus trifoliate are used as a medicine for the treatment of gastrointestinal disorders, inflammation, and allergies in East Asia. However, their effect on colon cancer cells remains unclear. We investigated the effect of the immature fruit of P. trifoliate extract on colorectal adenocarcinoma. The extract of the immature fruit of P. trifoliata inhibited the proliferation of CT-26 cells compared with untreated cells and it induced autophagy and apoptosis through the protein kinase B/mammalian target of rapamycin and 5′-AMP-activated protein kinase pathways. The number of autophagic vacuoles and autophage markers increased in response to the extract. At later time-points, apoptosis increased dose/time-dependently. In CT-26 cells pre-treated a pan-caspase inhibitor prior to P. trifoliata immature fruit extract treatment, we did not find any change in pro-caspase 3 and pro-PARP levels. Additionally, in cells pre-treated autphage inhibitor, SQSTM1/p62 and LC3AB, pro-caspase 3 and pro-PARP levels did not change. Our results indicate the molecular mechanisms that the extract of the immature fruit of P. trifoliata induces apoptosis in colorectal carcinoma cells by inducing mitochondrial autophagy. In this study, we provided a draft for further investigate the use of MEPT for colorectal cancer inhibition.http://www.sciencedirect.com/science/article/pii/S2213453020301397AnticancerAutophagyApoptosisMitochondriaPoncirus trifoliata
spellingShingle Sun-Young Kim
Ho-Keun Yi
Bong-Sik Yun
Dae-Yeol Lee
Pyung Han Hwang
Hae-Ryong Park
Min Sun Kim
The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
Food Science and Human Wellness
Anticancer
Autophagy
Apoptosis
Mitochondria
Poncirus trifoliata
title The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
title_full The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
title_fullStr The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
title_full_unstemmed The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
title_short The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
title_sort extract of the immature fruit of poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy
topic Anticancer
Autophagy
Apoptosis
Mitochondria
Poncirus trifoliata
url http://www.sciencedirect.com/science/article/pii/S2213453020301397
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