Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression
The natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the i...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Iman O. Sherif Laila A. Al-Mutabagani Dina Sabry Nehal M. Elsherbiny |
| author_facet | Iman O. Sherif Laila A. Al-Mutabagani Dina Sabry Nehal M. Elsherbiny |
| author_sort | Iman O. Sherif |
| collection | DOAJ |
| description | The natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the impact of chrysin on glypican-3 (GPC3)/sulfatase-2 (SULF2) axis and lncRNA-AF085935 expression in HCC using HepG2 cells. Cisplatin (20, 50, 100 μg/mL), chrysin (15, 30, and 60 μg/mL) and the combination of 50 μg/mL cisplatin with different concentrations of chrysin were applied for 24/48 h. Cell viability was determined by MTT assay. Protein levels of GPC3 and SULF2 were measured by ELISA at 24/48 h. GPC3 immunoreactivity was detected by immunocytochemistry. Moreover, GPC3 and SULF2 mRNA expressions in addition to lncRNA-AF085935 expression were assessed by qPCR at 48 h. The GPC3 protein, immunostaining and mRNA levels, SULF2 protein and mRNA levels, as well as lncRNA-AF085935 expression, were decreased significantly with cisplatin and chrysin alone when compared with the control untreated HepG2 cells. However, the combination treatment exhibited a better chemopreventive effect in a dose- and time-dependent manner. This study demonstrated, for the first time, the antiproliferative activity of chrysin against HCC through the suppression of the GPC3/SULF2 axis along with the downregulation of lncRNA-AF085935 expression. Synergistic effect of chrysin with cisplatin could potentiate their antiproliferative action in a dose- and time-dependent manner. |
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| last_indexed | 2024-03-10T15:35:35Z |
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| spelling | doaj.art-71dbb3080bd34fc6b4bd5ff4dfa9c64c2023-11-20T17:17:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120764210.3390/ijms21207642Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 ExpressionIman O. Sherif0Laila A. Al-Mutabagani1Dina Sabry2Nehal M. Elsherbiny3Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptChemistry Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi ArabiaMedical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11562, EgyptBiochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptThe natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the impact of chrysin on glypican-3 (GPC3)/sulfatase-2 (SULF2) axis and lncRNA-AF085935 expression in HCC using HepG2 cells. Cisplatin (20, 50, 100 μg/mL), chrysin (15, 30, and 60 μg/mL) and the combination of 50 μg/mL cisplatin with different concentrations of chrysin were applied for 24/48 h. Cell viability was determined by MTT assay. Protein levels of GPC3 and SULF2 were measured by ELISA at 24/48 h. GPC3 immunoreactivity was detected by immunocytochemistry. Moreover, GPC3 and SULF2 mRNA expressions in addition to lncRNA-AF085935 expression were assessed by qPCR at 48 h. The GPC3 protein, immunostaining and mRNA levels, SULF2 protein and mRNA levels, as well as lncRNA-AF085935 expression, were decreased significantly with cisplatin and chrysin alone when compared with the control untreated HepG2 cells. However, the combination treatment exhibited a better chemopreventive effect in a dose- and time-dependent manner. This study demonstrated, for the first time, the antiproliferative activity of chrysin against HCC through the suppression of the GPC3/SULF2 axis along with the downregulation of lncRNA-AF085935 expression. Synergistic effect of chrysin with cisplatin could potentiate their antiproliferative action in a dose- and time-dependent manner.https://www.mdpi.com/1422-0067/21/20/7642hepatocellular carcinomaChrysinGPC3SULF2lncRNA-AF085935 |
| spellingShingle | Iman O. Sherif Laila A. Al-Mutabagani Dina Sabry Nehal M. Elsherbiny Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression International Journal of Molecular Sciences hepatocellular carcinoma Chrysin GPC3 SULF2 lncRNA-AF085935 |
| title | Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression |
| title_full | Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression |
| title_fullStr | Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression |
| title_full_unstemmed | Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression |
| title_short | Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression |
| title_sort | antineoplastic activity of chrysin against human hepatocellular carcinoma new insight on gpc3 sulf2 axis and lncrna af085935 expression |
| topic | hepatocellular carcinoma Chrysin GPC3 SULF2 lncRNA-AF085935 |
| url | https://www.mdpi.com/1422-0067/21/20/7642 |
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