A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells
Abstract Prenylated flavonoids have been demonstrated to possess diverse bioactivities including antitumor effects. One new, daphnegiravone D (1), and four known (2–5) prenylated flavonoids were isolated from Daphne giraldii. Their cytotoxic activities revealed that daphnegiravone D markedly inhibit...
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05955-0 |
| _version_ | 1818421919648579584 |
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| author | Di Wang Qian Sun Jie Wu Wei Wang Guodong Yao Tianyang Li Xue Li Lingzhi Li Yan Zhang Wei Cui Shaojiang Song |
| author_facet | Di Wang Qian Sun Jie Wu Wei Wang Guodong Yao Tianyang Li Xue Li Lingzhi Li Yan Zhang Wei Cui Shaojiang Song |
| author_sort | Di Wang |
| collection | DOAJ |
| description | Abstract Prenylated flavonoids have been demonstrated to possess diverse bioactivities including antitumor effects. One new, daphnegiravone D (1), and four known (2–5) prenylated flavonoids were isolated from Daphne giraldii. Their cytotoxic activities revealed that daphnegiravone D markedly inhibited the proliferation of cancer cells, but had no apparent cytotoxicity on human normal cells. Mechanistically, daphnegiravone D induced G0/G1 arrest and apoptosis, reduced the expression of cyclin E1, CDK2 and CDK4, and promoted the cleavage of caspase 3 and PARP in Hep3B and HepG2 cells. Meanwhile, daphnegiravone D increased the level of phosphorylated p38 and attenuated phosphorylated JNK. Further studies indicated that SB203580 partially reversed daphnegiravone D-induced G0/G1 arrest and apoptosis. The addition of SP600125 to both cell lines increased the cleavage of caspase 3 and PARP, but did not affect the G0/G1 arrest. Besides, in vivo studies demonstrated that daphnegiravone D obviously inhibited tumor growth in a nude mouse xenograft model through suppressing the proliferation of tumor cells, without significant effect on body weight or pathology characteristics. Taken together, the new compound selectively inhibited the proliferation of hepatoma cells via p38 and JNK MAPK pathways, suggesting its potential as a novel natural anti-hepatocellular carcinoma agent. |
| first_indexed | 2024-12-14T13:18:01Z |
| format | Article |
| id | doaj.art-dc6fdcf421114c6499e0a116653ab36a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:18:01Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dc6fdcf421114c6499e0a116653ab36a2022-12-21T22:59:59ZengNature PortfolioScientific Reports2045-23222017-07-017111310.1038/s41598-017-05955-0A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cellsDi Wang0Qian Sun1Jie Wu2Wei Wang3Guodong Yao4Tianyang Li5Xue Li6Lingzhi Li7Yan Zhang8Wei Cui9Shaojiang Song10School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversitySchool of Life Science and Biopharmaceutics, Shenyang Pharmaceutical UniversitySchool of Life Science and Biopharmaceutics, Shenyang Pharmaceutical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversityKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversitySchool of Life Science and Biopharmaceutics, Shenyang Pharmaceutical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversityAbstract Prenylated flavonoids have been demonstrated to possess diverse bioactivities including antitumor effects. One new, daphnegiravone D (1), and four known (2–5) prenylated flavonoids were isolated from Daphne giraldii. Their cytotoxic activities revealed that daphnegiravone D markedly inhibited the proliferation of cancer cells, but had no apparent cytotoxicity on human normal cells. Mechanistically, daphnegiravone D induced G0/G1 arrest and apoptosis, reduced the expression of cyclin E1, CDK2 and CDK4, and promoted the cleavage of caspase 3 and PARP in Hep3B and HepG2 cells. Meanwhile, daphnegiravone D increased the level of phosphorylated p38 and attenuated phosphorylated JNK. Further studies indicated that SB203580 partially reversed daphnegiravone D-induced G0/G1 arrest and apoptosis. The addition of SP600125 to both cell lines increased the cleavage of caspase 3 and PARP, but did not affect the G0/G1 arrest. Besides, in vivo studies demonstrated that daphnegiravone D obviously inhibited tumor growth in a nude mouse xenograft model through suppressing the proliferation of tumor cells, without significant effect on body weight or pathology characteristics. Taken together, the new compound selectively inhibited the proliferation of hepatoma cells via p38 and JNK MAPK pathways, suggesting its potential as a novel natural anti-hepatocellular carcinoma agent.https://doi.org/10.1038/s41598-017-05955-0 |
| spellingShingle | Di Wang Qian Sun Jie Wu Wei Wang Guodong Yao Tianyang Li Xue Li Lingzhi Li Yan Zhang Wei Cui Shaojiang Song A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells Scientific Reports |
| title | A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells |
| title_full | A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells |
| title_fullStr | A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells |
| title_full_unstemmed | A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells |
| title_short | A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells |
| title_sort | new prenylated flavonoid induces g0 g1 arrest and apoptosis through p38 jnk mapk pathways in human hepatocellular carcinoma cells |
| url | https://doi.org/10.1038/s41598-017-05955-0 |
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