Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo
<b>Background:</b> Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, ranking fifth in terms of fatality with poor prognosis and a low survival rate. Rhoifolin (ROF), a flavonoid constituent, has previously been shown to suppress the proliferation of breast and pancrea...
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2025-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/18/1/79 |
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| author | Ruolan Chen Zufa Sabeel Lu Ying Youfeng Liang Rui Guo Mingxuan Hao Xiaoyang Chen Wenjing Zhang Jian Dong Yan Liu Changyuan Yu Zhao Yang |
| author_facet | Ruolan Chen Zufa Sabeel Lu Ying Youfeng Liang Rui Guo Mingxuan Hao Xiaoyang Chen Wenjing Zhang Jian Dong Yan Liu Changyuan Yu Zhao Yang |
| author_sort | Ruolan Chen |
| collection | DOAJ |
| description | <b>Background:</b> Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, ranking fifth in terms of fatality with poor prognosis and a low survival rate. Rhoifolin (ROF), a flavonoid constituent, has previously been shown to suppress the proliferation of breast and pancreatic cancer cells. However, its inhibitory effect on HCC has remained unexplored. <b>Objectives:</b> Exploring the potent inhibitory activities and underlying mechanisms of ROF on HCC cells. <b>Methods:</b> The suppressive effect of ROF on HCC cells were assessed via CCK8 assay, apoptosis assay, cell cycle analysis and xenograft tumor mouse model. Furthermore, quantitative real-time PCR and western blot were applied to analyze the underlying mechanisms of ROF on HCC cells. <b>Results:</b> Firstly, the IC<sub>50</sub> values of ROF in HepG2 and HuH7 cells were 373.9 and 288.7 µg/mL at 24 h and 208.9 and 218.0 µg/mL at 48 h, respectively. Moreover, the apoptosis rates of HepG2 and HuH7 cells increased from 6.63% and 6.59% to 17.61% and 21.83% at 24 h and increased from 6.63% and 6.59% to 30.04% and 37.90% at 48 h, respectively. Additionally, ROF induced cell cycle arrest at the S phase in HCC cells. Furthermore, ROF suppressed the tumor growth of HCC cells in vivo without obvious toxicity. Mechanically, ROF facilitated apoptosis by upregulating the expression of PIDD1, CASP8, CASP9, BID, BAX, BIM, and BAK1 in HCC cells. <b>Conclusions:</b> ROF significantly restrains the growth of HCC cells in vitro and in vivo, which could be an effective supplement for HCC therapy. |
| format | Article |
| id | doaj-art-81e052c8501e4fe9b48da2f120b65d88 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-81e052c8501e4fe9b48da2f120b65d882025-01-24T13:45:18ZengMDPI AGPharmaceuticals1424-82472025-01-011817910.3390/ph18010079Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In VivoRuolan Chen0Zufa Sabeel1Lu Ying2Youfeng Liang3Rui Guo4Mingxuan Hao5Xiaoyang Chen6Wenjing Zhang7Jian Dong8Yan Liu9Changyuan Yu10Zhao Yang11Innovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaInnovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China<b>Background:</b> Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, ranking fifth in terms of fatality with poor prognosis and a low survival rate. Rhoifolin (ROF), a flavonoid constituent, has previously been shown to suppress the proliferation of breast and pancreatic cancer cells. However, its inhibitory effect on HCC has remained unexplored. <b>Objectives:</b> Exploring the potent inhibitory activities and underlying mechanisms of ROF on HCC cells. <b>Methods:</b> The suppressive effect of ROF on HCC cells were assessed via CCK8 assay, apoptosis assay, cell cycle analysis and xenograft tumor mouse model. Furthermore, quantitative real-time PCR and western blot were applied to analyze the underlying mechanisms of ROF on HCC cells. <b>Results:</b> Firstly, the IC<sub>50</sub> values of ROF in HepG2 and HuH7 cells were 373.9 and 288.7 µg/mL at 24 h and 208.9 and 218.0 µg/mL at 48 h, respectively. Moreover, the apoptosis rates of HepG2 and HuH7 cells increased from 6.63% and 6.59% to 17.61% and 21.83% at 24 h and increased from 6.63% and 6.59% to 30.04% and 37.90% at 48 h, respectively. Additionally, ROF induced cell cycle arrest at the S phase in HCC cells. Furthermore, ROF suppressed the tumor growth of HCC cells in vivo without obvious toxicity. Mechanically, ROF facilitated apoptosis by upregulating the expression of PIDD1, CASP8, CASP9, BID, BAX, BIM, and BAK1 in HCC cells. <b>Conclusions:</b> ROF significantly restrains the growth of HCC cells in vitro and in vivo, which could be an effective supplement for HCC therapy.https://www.mdpi.com/1424-8247/18/1/79rhoifolinhepatocellular carcinomaapoptosiscell cycle arrestBID |
| spellingShingle | Ruolan Chen Zufa Sabeel Lu Ying Youfeng Liang Rui Guo Mingxuan Hao Xiaoyang Chen Wenjing Zhang Jian Dong Yan Liu Changyuan Yu Zhao Yang Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo Pharmaceuticals rhoifolin hepatocellular carcinoma apoptosis cell cycle arrest BID |
| title | Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo |
| title_full | Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo |
| title_fullStr | Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo |
| title_full_unstemmed | Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo |
| title_short | Rhoifolin Suppresses Cell Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells In Vitro and In Vivo |
| title_sort | rhoifolin suppresses cell proliferation and induces apoptosis in hepatocellular carcinoma cells in vitro and in vivo |
| topic | rhoifolin hepatocellular carcinoma apoptosis cell cycle arrest BID |
| url | https://www.mdpi.com/1424-8247/18/1/79 |
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