Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway
Hepatocellular carcinoma is the most common type of primary liver cancer in humans. This study aimed to demonstrate anticancer properties of an aqueous extract from Chrysophyllum cainito stem bark (CE) and its underlying mechanisms. Our MTT assay results showed that CE significantly reduced human he...
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PeerJ Inc.
2020-10-01
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| Online Access: | https://peerj.com/articles/10168.pdf |
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| author | Hau V. Doan Pishyaporn Sritangos Roongtip Iyara Nuannoi Chudapongse |
| author_facet | Hau V. Doan Pishyaporn Sritangos Roongtip Iyara Nuannoi Chudapongse |
| author_sort | Hau V. Doan |
| collection | DOAJ |
| description | Hepatocellular carcinoma is the most common type of primary liver cancer in humans. This study aimed to demonstrate anticancer properties of an aqueous extract from Chrysophyllum cainito stem bark (CE) and its underlying mechanisms. Our MTT assay results showed that CE significantly reduced human hepatocellular carcinoma (HepG2) cell viability with the IC50of 100 µg/mL, while human dermal primary fibroblast (HDFa) cells showed less susceptibility in every concentration tested. Determined by Annexin V staining, the proportion of apoptotic HepG2 cells increased in a dose-dependent fashion after 24 hour-exposure of CE. The results from Western blot analysis confirmed that CE reduced procaspase-3, suggesting apoptosis by activating caspase-3 cleavage. Using the DCFH-DA and DiOC6 fluorescent probes, it was found that CE significantly stimulated the generation of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (Δψ m), respectively. According to cell cycle analysis, CE (100 µg/mL) profoundly increased the percentage of cells in the sub-G1 phase, indicating cell apoptosis. These data suggest that CE induces apoptosis and cell death in human hepatocellular carcinoma via generation of intracellular ROS and disruption of Δψm. This is the first demonstration of the anticancer activity with proposed underlying mechanism of CE in liver cancer cells. |
| first_indexed | 2024-03-09T08:05:02Z |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:05:02Z |
| publishDate | 2020-10-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-f8ba1ec377754c37bcc583d4f588893d2023-12-03T00:24:52ZengPeerJ Inc.PeerJ2167-83592020-10-018e1016810.7717/peerj.10168Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathwayHau V. Doan0Pishyaporn Sritangos1Roongtip Iyara2Nuannoi Chudapongse3Department of Pharmacy, School of Medicine and Pharmacy, Tra Vinh University, Tra Vinh, VietnamSchool of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Muang, Nakhon Ratchasima, ThailandSchool of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Muang, Nakhon Ratchasima, ThailandSchool of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Muang, Nakhon Ratchasima, ThailandHepatocellular carcinoma is the most common type of primary liver cancer in humans. This study aimed to demonstrate anticancer properties of an aqueous extract from Chrysophyllum cainito stem bark (CE) and its underlying mechanisms. Our MTT assay results showed that CE significantly reduced human hepatocellular carcinoma (HepG2) cell viability with the IC50of 100 µg/mL, while human dermal primary fibroblast (HDFa) cells showed less susceptibility in every concentration tested. Determined by Annexin V staining, the proportion of apoptotic HepG2 cells increased in a dose-dependent fashion after 24 hour-exposure of CE. The results from Western blot analysis confirmed that CE reduced procaspase-3, suggesting apoptosis by activating caspase-3 cleavage. Using the DCFH-DA and DiOC6 fluorescent probes, it was found that CE significantly stimulated the generation of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (Δψ m), respectively. According to cell cycle analysis, CE (100 µg/mL) profoundly increased the percentage of cells in the sub-G1 phase, indicating cell apoptosis. These data suggest that CE induces apoptosis and cell death in human hepatocellular carcinoma via generation of intracellular ROS and disruption of Δψm. This is the first demonstration of the anticancer activity with proposed underlying mechanism of CE in liver cancer cells.https://peerj.com/articles/10168.pdfChrysophyllum cainitoApoptosisHepatocellular carcinomaReactive oxygen speciesCell cyclesHepG2 cell |
| spellingShingle | Hau V. Doan Pishyaporn Sritangos Roongtip Iyara Nuannoi Chudapongse Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway PeerJ Chrysophyllum cainito Apoptosis Hepatocellular carcinoma Reactive oxygen species Cell cycles HepG2 cell |
| title | Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway |
| title_full | Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway |
| title_fullStr | Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway |
| title_full_unstemmed | Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway |
| title_short | Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway |
| title_sort | chrysophyllum cainito stem bark extract induces apoptosis in human hepatocarcinoma hepg2 cells through ros mediated mitochondrial pathway |
| topic | Chrysophyllum cainito Apoptosis Hepatocellular carcinoma Reactive oxygen species Cell cycles HepG2 cell |
| url | https://peerj.com/articles/10168.pdf |
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