Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33)
Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 c...
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Elsevier
2023-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023010502 |
| _version_ | 1797851898358792192 |
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| author | Cuiting Lv Aihua Lan Xiao Fan Caiguo Huang Gong Yang |
| author_facet | Cuiting Lv Aihua Lan Xiao Fan Caiguo Huang Gong Yang |
| author_sort | Cuiting Lv |
| collection | DOAJ |
| description | Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug. |
| first_indexed | 2024-04-09T19:25:17Z |
| format | Article |
| id | doaj.art-2646e29d4d4149c6a8377aa33e40421b |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T19:25:17Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-2646e29d4d4149c6a8377aa33e40421b2023-04-05T08:17:24ZengElsevierHeliyon2405-84402023-03-0193e13843Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33)Cuiting Lv0Aihua Lan1Xiao Fan2Caiguo Huang3Gong Yang4Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, ChinaDepartment of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 201900, China; Corresponding author. Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, 280 Mohe Road, Shanghai, 201900, China.Department of Biochemistry and Molecular Biology, College of Basic Medical, Naval Medical University, Shanghai, 200433, China; Corresponding author. Department of Biochemistry and Molecular Biology, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, 200032, China; Corresponding author. Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Shanghai, 200240, China.Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug.http://www.sciencedirect.com/science/article/pii/S2405844023010502Asperolide AHepatoma cellCell cycle arrestApoptosisMAPKp53 mutation |
| spellingShingle | Cuiting Lv Aihua Lan Xiao Fan Caiguo Huang Gong Yang Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33) Heliyon Asperolide A Hepatoma cell Cell cycle arrest Apoptosis MAPK p53 mutation |
| title | Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33) |
| title_full | Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33) |
| title_fullStr | Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33) |
| title_full_unstemmed | Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33) |
| title_short | Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33) |
| title_sort | asperolide a induces apoptosis and cell cycle arrest of human hepatoma cells with p53 y220c mutant through p38 mediating phosphorylation of p53 s33 |
| topic | Asperolide A Hepatoma cell Cell cycle arrest Apoptosis MAPK p53 mutation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023010502 |
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