Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis
Abstract Background Malignant transformation from hepatic fibrosis to carcinogenesis may be a therapeutic target for hepatocellular carcinoma (HCC). The aim of this study was to evaluate anti-cancer efficacy of Pien-Tze-Huang (PZH), and to investigate the underlying mechanisms by integrating transcr...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-023-02946-2 |
| _version_ | 1797806533975736320 |
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| author | Xiangying Yan Yudong Liu Congchong Li Xia Mao Tengteng Xu Zhixing Hu Chu Zhang Na Lin Ya Lin Yanqiong Zhang |
| author_facet | Xiangying Yan Yudong Liu Congchong Li Xia Mao Tengteng Xu Zhixing Hu Chu Zhang Na Lin Ya Lin Yanqiong Zhang |
| author_sort | Xiangying Yan |
| collection | DOAJ |
| description | Abstract Background Malignant transformation from hepatic fibrosis to carcinogenesis may be a therapeutic target for hepatocellular carcinoma (HCC). The aim of this study was to evaluate anti-cancer efficacy of Pien-Tze-Huang (PZH), and to investigate the underlying mechanisms by integrating transcriptional regulatory network analysis and experimental validation. Methods A diethylnitrosamine (DEN)-induced HCC model in rats was established and used to evaluate the anti-cancer efficacy of PZH. After detecting a transcriptomic profiling, the “disease-related gene–drug effective target” interaction network was constructed, and the candidate targets of PZH against malignant transformation from hepatic fibrosis to HCC were identified and verified in vitro. Results PZH effectively alleviated the pathological changes of hepatic fibrosis and cirrhosis, and inhibited tumor formation and growth in DEN-induced HCC rats. Additionally, the administration of PZH reduced the levels of various hepatic function-related serological indicators significantly. Mechanically, a ferroptosis-related SLC7A11-GSH-GPX4 axis might be one of potential targets of PZH against malignant transformation from hepatic fibrosis to HCC. Especially, high SLC7A11 expression may be associated with poor prognosis of HCC patients. Experimentally, the administration of PZH markedly increased the trivalent iron and ferrous ion, suppressed the expression levels of SLC7A11 and GPX4 proteins, and reduced the GSH/GSSG ratio in the liver tissues of DEN-induced HCC rats. Conclusions Our data offer an evidence that PZH may effectively improve the hepatic fibrosis microenvironment and prevent the occurrence of HCC through promoting ferroptosis in tumor cells via inhibiting the SLC7A11-GSH-GPX4 axis, implying that PZH may be a potential candidate drug for prevention and treatment of HCC at an early stage. |
| first_indexed | 2024-03-13T06:08:42Z |
| format | Article |
| id | doaj.art-b0d4ab78739146fc887c95eccc275a55 |
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| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-13T06:08:42Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-b0d4ab78739146fc887c95eccc275a552023-06-11T11:25:47ZengBMCCancer Cell International1475-28672023-06-0123111410.1186/s12935-023-02946-2Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axisXiangying Yan0Yudong Liu1Congchong Li2Xia Mao3Tengteng Xu4Zhixing Hu5Chu Zhang6Na Lin7Ya Lin8Yanqiong Zhang9College of Pharmacy, Fujian University of Traditional Chinese MedicineInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesCollege of Pharmacy, Fujian University of Traditional Chinese MedicineInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesCollege of Pharmacy, Fujian University of Traditional Chinese MedicineCollege of Pharmacy, Fujian University of Traditional Chinese MedicineInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesCollege of Pharmacy, Fujian University of Traditional Chinese MedicineCollege of Pharmacy, Fujian University of Traditional Chinese MedicineAbstract Background Malignant transformation from hepatic fibrosis to carcinogenesis may be a therapeutic target for hepatocellular carcinoma (HCC). The aim of this study was to evaluate anti-cancer efficacy of Pien-Tze-Huang (PZH), and to investigate the underlying mechanisms by integrating transcriptional regulatory network analysis and experimental validation. Methods A diethylnitrosamine (DEN)-induced HCC model in rats was established and used to evaluate the anti-cancer efficacy of PZH. After detecting a transcriptomic profiling, the “disease-related gene–drug effective target” interaction network was constructed, and the candidate targets of PZH against malignant transformation from hepatic fibrosis to HCC were identified and verified in vitro. Results PZH effectively alleviated the pathological changes of hepatic fibrosis and cirrhosis, and inhibited tumor formation and growth in DEN-induced HCC rats. Additionally, the administration of PZH reduced the levels of various hepatic function-related serological indicators significantly. Mechanically, a ferroptosis-related SLC7A11-GSH-GPX4 axis might be one of potential targets of PZH against malignant transformation from hepatic fibrosis to HCC. Especially, high SLC7A11 expression may be associated with poor prognosis of HCC patients. Experimentally, the administration of PZH markedly increased the trivalent iron and ferrous ion, suppressed the expression levels of SLC7A11 and GPX4 proteins, and reduced the GSH/GSSG ratio in the liver tissues of DEN-induced HCC rats. Conclusions Our data offer an evidence that PZH may effectively improve the hepatic fibrosis microenvironment and prevent the occurrence of HCC through promoting ferroptosis in tumor cells via inhibiting the SLC7A11-GSH-GPX4 axis, implying that PZH may be a potential candidate drug for prevention and treatment of HCC at an early stage.https://doi.org/10.1186/s12935-023-02946-2Hepatocellular carcinomaPien-Tze-HuangFerroptosisSolute carrier family 7 member 11GlutathioneGlutathione peroxidase 4 |
| spellingShingle | Xiangying Yan Yudong Liu Congchong Li Xia Mao Tengteng Xu Zhixing Hu Chu Zhang Na Lin Ya Lin Yanqiong Zhang Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis Cancer Cell International Hepatocellular carcinoma Pien-Tze-Huang Ferroptosis Solute carrier family 7 member 11 Glutathione Glutathione peroxidase 4 |
| title | Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis |
| title_full | Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis |
| title_fullStr | Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis |
| title_full_unstemmed | Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis |
| title_short | Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis |
| title_sort | pien tze huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting slc7a11 gsh gpx4 axis |
| topic | Hepatocellular carcinoma Pien-Tze-Huang Ferroptosis Solute carrier family 7 member 11 Glutathione Glutathione peroxidase 4 |
| url | https://doi.org/10.1186/s12935-023-02946-2 |
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