This study is all about Liver cancer is the fatal cause of cancer deaths worldwide due to its aggressiveness and lack of effective therapies. Tiliroside (C30H26O13) is an active compound extracted from herb plant Tribulus terrestris L., which has been used as alternative therapy in clinic practice. However, its therapeutic use against liver cancer has not been previously reported. Here, we showed that Tiliroside exerted significantly higher anti-proliferation effect on liver cancer cell lines Hep3B and SNU-449 than on liver normal cell THLE-3 cells or NC group, respectively, by using MTS assay. Results from colony formation, immigration and invasion assays support the anticancer efficacy of Tiliroside and its low-toxic property while treating liver normal cell THLE-3. 3D spheroid formation and CD133expression level also displays its anti-stemness effect.
Fig: Tiliroside inhibited the proliferation and colony formation of Hep3B and SNU-449 cells and the restoration by CAXII overexpression. Relative inhibition rates of Hep3B, SNU-449 and also THLE-3 in response to different concentrations of Tiliroside were calculated by comparing the OD value of NC, at 24, 48, 72, and 96 h, respectively (A–C). The representative colony formation of Hep3B and SNU-449 cells intervened by 40 μM Tiliroside and NC (H). The relative colony formation efficiency showed significant reduction of colony 10 days afterTiliroside intervention in both Hep3B and SNU-449 cells (F). The relative CAXIIexpression was significantly higher in CAXII-transfection group than non-transfection group in both Hep3B and SNU-449 cell lines (D). The relative CAXIIexpression was significantly decreased in CAXII-KO group than none transfection group in both Hep3B and SNU-449 cell lines (E). The inhibition rates brought by Tiliroside were significantly increased in CAXII overexpression group compared to both non-transfection group and empty vector group, at 48 and 72 h, respectviely, in Hep3B and SNU-449 cells. On the contrary, The inhibition rates were significantly decreased in CAXII-KO group compared to both non-transfection group and none-KO group, at 24, 48 and 72 h, respectviely in both cell lines (E). Data are presented as the mean ± standard deviation (SD); NS not significant, NC negative control.
It has been showed that Tiliroside may function as Carbonic anhydrases XII (CAXII) inhibitor and affects apoptotic E2F1/E2F3/Caspase-3 axis by using CAXII esterase activity assay, Human carbonic anhydrase 12 (CA-12) ELISA Kit, quantitative reverse transcription PCR (RT-qPCR) as well as CaspACE Assay System, respectively. In summary, we demonstrate for the first time thatTiliroside suppresses liver cancer development possibly by acting as a novel CAXII inhibitor, which warrant further investigation on its therapeutic implications.
Han, R., Yang, H., Lu, L. et al. Tiliroside as a CAXII inhibitor suppresses liver cancer development and modulates E2Fs/Caspase-3 axis. Sci Rep11, 8626 (2021). https://doi.org/10.1038/s41598-021-88133-7