Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells
Studies have indicated that Na<sup>+</sup>-<span style="font-variant: small-caps;">d</span>-glucose co-transporter (SGLT) inhibitors had anti-proliferative activity by attenuating the uptake of glucose in several tumor cell lines. In this study, the molecular dockin...
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MDPI AG
2019-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/18/3390 |
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| author | Lujing Wang Min Liu Fei Yin Yuanqiang Wang Xingan Li Yucui Wu Cuilian Ye Jianhui Liu |
| author_facet | Lujing Wang Min Liu Fei Yin Yuanqiang Wang Xingan Li Yucui Wu Cuilian Ye Jianhui Liu |
| author_sort | Lujing Wang |
| collection | DOAJ |
| description | Studies have indicated that Na<sup>+</sup>-<span style="font-variant: small-caps;">d</span>-glucose co-transporter (SGLT) inhibitors had anti-proliferative activity by attenuating the uptake of glucose in several tumor cell lines. In this study, the molecular docking showed that, trilobatin, one of the dihydrochalcones from leaves of <i>Lithocarpus polystachyus</i> Rehd., might be a novel inhibitor of SGLT1 and SGLT2, which evidently attenuated the uptake of glucose in vitro and in vivo. To our surprise, we observed that trilobatin did not inhibit, but promoted the proliferation of human hepatoblastoma HepG2 and Huh 7 cells when it was present at high concentrations. At the same time, incubation with high concentrations of trilobatin arrested the cell cycle at S phase in HepG2 cells. We also found that treatment with trilobatin had no significant effect on the expression of hepatitis B x-interacting protein (HBXIP) and hepatocyte nuclear factor (HNF)-4α, the two key regulators of hepatocyte proliferation. Taken together, although trilobatin worked as a novel inhibitor of SGLTs to attenuate the uptake of glucose, it also selectively induced the cell proliferation of HepG2 cells, suggesting that not all the SGLT inhibitors inhibited the proliferation of tumor cells, and further studies are needed to assess the anti-cancer potentials of new glucose-lowering agents. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T05:01:26Z |
| publishDate | 2019-09-01 |
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| series | Molecules |
| spelling | doaj.art-f6289363df664c9cb4ca29b45f49cff22022-12-21T19:15:15ZengMDPI AGMolecules1420-30492019-09-012418339010.3390/molecules24183390molecules24183390Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma CellsLujing Wang0Min Liu1Fei Yin2Yuanqiang Wang3Xingan Li4Yucui Wu5Cuilian Ye6Jianhui Liu7Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaChongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing 400054, ChinaStudies have indicated that Na<sup>+</sup>-<span style="font-variant: small-caps;">d</span>-glucose co-transporter (SGLT) inhibitors had anti-proliferative activity by attenuating the uptake of glucose in several tumor cell lines. In this study, the molecular docking showed that, trilobatin, one of the dihydrochalcones from leaves of <i>Lithocarpus polystachyus</i> Rehd., might be a novel inhibitor of SGLT1 and SGLT2, which evidently attenuated the uptake of glucose in vitro and in vivo. To our surprise, we observed that trilobatin did not inhibit, but promoted the proliferation of human hepatoblastoma HepG2 and Huh 7 cells when it was present at high concentrations. At the same time, incubation with high concentrations of trilobatin arrested the cell cycle at S phase in HepG2 cells. We also found that treatment with trilobatin had no significant effect on the expression of hepatitis B x-interacting protein (HBXIP) and hepatocyte nuclear factor (HNF)-4α, the two key regulators of hepatocyte proliferation. Taken together, although trilobatin worked as a novel inhibitor of SGLTs to attenuate the uptake of glucose, it also selectively induced the cell proliferation of HepG2 cells, suggesting that not all the SGLT inhibitors inhibited the proliferation of tumor cells, and further studies are needed to assess the anti-cancer potentials of new glucose-lowering agents.https://www.mdpi.com/1420-3049/24/18/3390Anti-tumorNa<sup>+</sup>-<span style="font-variant: small-caps">d</span>-glucose co-transporter (SGLT) inhibitorsCell proliferationTrilobatin |
| spellingShingle | Lujing Wang Min Liu Fei Yin Yuanqiang Wang Xingan Li Yucui Wu Cuilian Ye Jianhui Liu Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells Molecules Anti-tumor Na<sup>+</sup>-<span style="font-variant: small-caps">d</span>-glucose co-transporter (SGLT) inhibitors Cell proliferation Trilobatin |
| title | Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells |
| title_full | Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells |
| title_fullStr | Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells |
| title_full_unstemmed | Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells |
| title_short | Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells |
| title_sort | trilobatin a novel sglt1 2 inhibitor selectively induces the proliferation of human hepatoblastoma cells |
| topic | Anti-tumor Na<sup>+</sup>-<span style="font-variant: small-caps">d</span>-glucose co-transporter (SGLT) inhibitors Cell proliferation Trilobatin |
| url | https://www.mdpi.com/1420-3049/24/18/3390 |
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