Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1
ABSTRACTHepatocellular carcinoma (HCC) is a frequently occurring malignant gastrointestinal cancer. The 5-year survival rate of HCC is still below 8%, and thus, identifying more effective therapeutic methods is needed. Here, we evaluated the effects of Stigmast-4-en-6β-ol-3-one (S463) on the viabili...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Animal Cells and Systems |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19768354.2023.2282224 |
| _version_ | 1797361642934108160 |
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| author | Zhiyun Zhang Jian Wang Weiping Wan Zhengchao Shen Aixue Zuo Rong Chen Qinyi Wu Enli Cai Feng Huang Rongping Zhang Xinan Shi |
| author_facet | Zhiyun Zhang Jian Wang Weiping Wan Zhengchao Shen Aixue Zuo Rong Chen Qinyi Wu Enli Cai Feng Huang Rongping Zhang Xinan Shi |
| author_sort | Zhiyun Zhang |
| collection | DOAJ |
| description | ABSTRACTHepatocellular carcinoma (HCC) is a frequently occurring malignant gastrointestinal cancer. The 5-year survival rate of HCC is still below 8%, and thus, identifying more effective therapeutic methods is needed. Here, we evaluated the effects of Stigmast-4-en-6β-ol-3-one (S463) on the viability and colony formation of liver cancer cells. S463 treatment decreased the viability and induced apoptosis and ferroptosis in liver cancer cells, and also increased cellular malondialdehyde (MDA) and lipid peroxidation levels. In S463 treated cells, the expression level of Bax was increased, and the expression level of GPX4 was reduced, and the cleavage of PARP was improved. We also found that S463 treatment downregulated E2F1 and upregulated p53 at both the mRNA and protein levels. Importantly, rescue experiments revealed that overexpression of E2F1 partially restored S463-induced Bax and p53 upregulation and GPX4 downregulation and counteracted the S463-induced decrease in cell viability and colony formation and the S463-induced increase in MDA and lipid peroxidation levels. Our findings suggest that S463 significantly inhibits viability and colony formation and induces apoptosis and ferroptosis in liver cancer cells via E2F1. |
| first_indexed | 2024-03-08T15:57:37Z |
| format | Article |
| id | doaj.art-7bb87bed2c1c417bad8c90e69e739d34 |
| institution | Directory Open Access Journal |
| issn | 1976-8354 2151-2485 |
| language | English |
| last_indexed | 2024-03-08T15:57:37Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Animal Cells and Systems |
| spelling | doaj.art-7bb87bed2c1c417bad8c90e69e739d342024-01-08T17:12:29ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852023-12-0127134035210.1080/19768354.2023.2282224Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1Zhiyun Zhang0Jian Wang1Weiping Wan2Zhengchao Shen3Aixue Zuo4Rong Chen5Qinyi Wu6Enli Cai7Feng Huang8Rongping Zhang9Xinan Shi10Department of Anorectal, The third Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, People’s Republic of ChinaThe First Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, People’s Republic of ChinaDepartment of Anorectal, The third Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, People’s Republic of ChinaSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaSchool of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaYunnan Key Laboratory of Molecular Biology of Chinese Medicine, Yunnan University of Chinese Medicine , Kunming, People’s Republic of ChinaDepartment of Nursing, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, People’s Republic of ChinaABSTRACTHepatocellular carcinoma (HCC) is a frequently occurring malignant gastrointestinal cancer. The 5-year survival rate of HCC is still below 8%, and thus, identifying more effective therapeutic methods is needed. Here, we evaluated the effects of Stigmast-4-en-6β-ol-3-one (S463) on the viability and colony formation of liver cancer cells. S463 treatment decreased the viability and induced apoptosis and ferroptosis in liver cancer cells, and also increased cellular malondialdehyde (MDA) and lipid peroxidation levels. In S463 treated cells, the expression level of Bax was increased, and the expression level of GPX4 was reduced, and the cleavage of PARP was improved. We also found that S463 treatment downregulated E2F1 and upregulated p53 at both the mRNA and protein levels. Importantly, rescue experiments revealed that overexpression of E2F1 partially restored S463-induced Bax and p53 upregulation and GPX4 downregulation and counteracted the S463-induced decrease in cell viability and colony formation and the S463-induced increase in MDA and lipid peroxidation levels. Our findings suggest that S463 significantly inhibits viability and colony formation and induces apoptosis and ferroptosis in liver cancer cells via E2F1.https://www.tandfonline.com/doi/10.1080/19768354.2023.2282224Stigmast-4-en-6β-ol-3-oneliver cancerapoptosisferroptosisE2F1 |
| spellingShingle | Zhiyun Zhang Jian Wang Weiping Wan Zhengchao Shen Aixue Zuo Rong Chen Qinyi Wu Enli Cai Feng Huang Rongping Zhang Xinan Shi Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1 Animal Cells and Systems Stigmast-4-en-6β-ol-3-one liver cancer apoptosis ferroptosis E2F1 |
| title | Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1 |
| title_full | Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1 |
| title_fullStr | Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1 |
| title_full_unstemmed | Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1 |
| title_short | Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1 |
| title_sort | stigmast 4 en 6β ol 3 one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing e2f1 |
| topic | Stigmast-4-en-6β-ol-3-one liver cancer apoptosis ferroptosis E2F1 |
| url | https://www.tandfonline.com/doi/10.1080/19768354.2023.2282224 |
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