Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells

Studies have indicated that Na⁺-d-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 Lithocarpus polystachyus 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. View Full-Text

Keywords: Anti-tumor; Na⁺-d-glucose co-transporter (SGLT) inhibitors; Cell proliferation; Trilobatin

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MDPI and ACS Style

Wang, L.; Liu, M.; Yin, F.; Wang, Y.; Li, X.; Wu, Y.; Ye, C.; Liu, J. Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells. Molecules 2019, 24, 3390. https://doi.org/10.3390/molecules24183390

AMA Style

Wang L, Liu M, Yin F, Wang Y, Li X, Wu Y, Ye C, Liu J. Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells. Molecules. 2019; 24(18):3390. https://doi.org/10.3390/molecules24183390

Chicago/Turabian Style

Wang, Lujing, Min Liu, Fei Yin, Yuanqiang Wang, Xingan Li, Yucui Wu, Cuilian Ye, and Jianhui Liu. 2019. "Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells" Molecules 24, no. 18: 3390. https://doi.org/10.3390/molecules24183390

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Trilobatin, a Novel SGLT1/2 Inhibitor, Selectively Induces the Proliferation of Human Hepatoblastoma Cells

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