Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells
This study was aimed at investigating the anti-cancer effect of bitter orange peel extract (BOPE) on Hep3B, a human hepatoma cell line. Upon treatment of Hep3B cells with 6.25–100 μg/mL of BOPE for 72 h, its antiproliferative effect was shown to increase in a concentration- and time-dependent manner...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464619303214 |
| _version_ | 1823940439803166720 |
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| author | Kuan-Hung Lu Huey-Yin Lee Yung-Lin Chu Chi-Tang Ho Lee-Yan Sheen |
| author_facet | Kuan-Hung Lu Huey-Yin Lee Yung-Lin Chu Chi-Tang Ho Lee-Yan Sheen |
| author_sort | Kuan-Hung Lu |
| collection | DOAJ |
| description | This study was aimed at investigating the anti-cancer effect of bitter orange peel extract (BOPE) on Hep3B, a human hepatoma cell line. Upon treatment of Hep3B cells with 6.25–100 μg/mL of BOPE for 72 h, its antiproliferative effect was shown to increase in a concentration- and time-dependent manner. The observations, such as concentration-dependent elevation of LC3 fluorescent puncta, increased conversion of LC3-I to LC3-II, no characteristic apoptotic nuclear fragmentation, and no significant effect on percentages of annexin V-positive apoptotic cells, confirmed the autophagy triggered by BOPE in Hep3B cells. Moreover, BOPE promoted ROS generation and induced endoplasmic reticulum stress through calcium ion-related AMPK/TSC2/mTOR and DAPK/Beclin-1 pathways, leading to autophagic cell death. Furthermore, our analysis showed that the major components of BOPE, tangeretin and nobiletin, exhibited a synergistic effect on the growth inhibition of Hep3B cells. Thus, these results suggest that BOPE may be used as a functional food against liver cancer. |
| first_indexed | 2024-12-17T04:13:28Z |
| format | Article |
| id | doaj.art-5296a379a210426f8603fcfd7dc6ce2a |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-17T04:13:28Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-5296a379a210426f8603fcfd7dc6ce2a2022-12-21T22:04:07ZengElsevierJournal of Functional Foods1756-46462019-09-0160Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cellsKuan-Hung Lu0Huey-Yin Lee1Yung-Lin Chu2Chi-Tang Ho3Lee-Yan Sheen4Institute of Food Science and Technology, National Taiwan University, Taipei 10617, TaiwanInstitute of Food Science and Technology, National Taiwan University, Taipei 10617, TaiwanDepartment of Food Science, Agricultural College, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan; International Master's Degree Program in Food Science, International College, National Pingtung University of Science and Technology, Pingtung 91201, TaiwanDepartment of Food Science, Rutgers University, New Brunswick, NJ 08901, USAInstitute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan; Center for Food and Biomolecules, National Taiwan University, Taipei 10617, Taiwan; National Center for Food Safety Education and Research, National Taiwan University, Taipei 10617, Taiwan; Corresponding author at: Institute of Food Science and Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan.This study was aimed at investigating the anti-cancer effect of bitter orange peel extract (BOPE) on Hep3B, a human hepatoma cell line. Upon treatment of Hep3B cells with 6.25–100 μg/mL of BOPE for 72 h, its antiproliferative effect was shown to increase in a concentration- and time-dependent manner. The observations, such as concentration-dependent elevation of LC3 fluorescent puncta, increased conversion of LC3-I to LC3-II, no characteristic apoptotic nuclear fragmentation, and no significant effect on percentages of annexin V-positive apoptotic cells, confirmed the autophagy triggered by BOPE in Hep3B cells. Moreover, BOPE promoted ROS generation and induced endoplasmic reticulum stress through calcium ion-related AMPK/TSC2/mTOR and DAPK/Beclin-1 pathways, leading to autophagic cell death. Furthermore, our analysis showed that the major components of BOPE, tangeretin and nobiletin, exhibited a synergistic effect on the growth inhibition of Hep3B cells. Thus, these results suggest that BOPE may be used as a functional food against liver cancer.http://www.sciencedirect.com/science/article/pii/S1756464619303214Hepatocellular carcinomaBitter orange peel extractPolymethoxyflavonesAutophagyCombination effect |
| spellingShingle | Kuan-Hung Lu Huey-Yin Lee Yung-Lin Chu Chi-Tang Ho Lee-Yan Sheen Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells Journal of Functional Foods Hepatocellular carcinoma Bitter orange peel extract Polymethoxyflavones Autophagy Combination effect |
| title | Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells |
| title_full | Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells |
| title_fullStr | Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells |
| title_full_unstemmed | Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells |
| title_short | Bitter orange peel extract induces endoplasmic reticulum-mediated autophagy in human hepatoma cells |
| title_sort | bitter orange peel extract induces endoplasmic reticulum mediated autophagy in human hepatoma cells |
| topic | Hepatocellular carcinoma Bitter orange peel extract Polymethoxyflavones Autophagy Combination effect |
| url | http://www.sciencedirect.com/science/article/pii/S1756464619303214 |
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