alisol-b-monoacetate and Liver-Neoplasms

Liver cancer seriously threatens the health of people. Meanwhile, it has been reported that bufalin could act as an inhibitor in liver cancer. In addition, alisol B 23-acetate is a natural product derived from. In order to detect the effect of alisol B 23-acetate in combination with bufalin on liver cancer, human liver cancer SMMC-7721 and MHCC97 cells were used as subjects. Bufalin and alisol B 23-acetate were performed on cells. Cell viability was tested by MTT assay. In addition, flow cytometry was performed to assess the cell apoptosis. Autophagy-related protein levels were tested by western blotting.. The data revealed that bufalin significantly decreased the viability of liver cancer cells, and the inhibitory effect was further increased by alisol B 23-acetate. In addition, alisol B 23-acetate notably enhanced the apoptotic effect of bufalin on liver cancer cells through mediation of Mcl-1, Bax, Bcl-2, and cleaved caspase-3. Meanwhile, alisol B 23-acetate in combination with bufalin induced the autophagy in liver cancer cells through mediation of Beclin-1 and p62. Furthermore, alisol B 23-acetate in combination with bufalin significantly downregulated the level of GSK-3. In summary, these findings provide the first evidence that alisol B 23-acetate improves the anticancer activity of bufalin on liver cancer through activation of the Wnt/

Topics: Apoptosis; beta Catenin; Bufanolides; Cell Line, Tumor; Cholestenones; Glycogen Synthase Kinase 3 beta; Humans; Liver Neoplasms

Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from Chinese herbal medicine and has a variety of biological functions, especially anti-cancer effects. However, the effects and mechanisms of AB23A in hepatocellular carcinoma (HCC) remain unclear. Cell viability, invasion and migration were measured by MTT, Transwell and wound healing assays, respectively. To detect cell cycle and apoptosis, a flow cytometry assay was used. Tumor xenograft experiment was performed to measure tumor growth. The enzymatic assay was used to determine the activity of matrix metalloproteinase (MMP)-2 and -9. Furthermore, the mRNA and protein levels of Bcl-2, Bax, Caspase-3/-9, MMP-2/-9 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) were detected by RT-PCR and Western blotting assays. AB23A suppressed cell viability in a concentration-dependent manner, blocked cell cycle, and induced apoptosis via up-regulating Bax, Caspase-3 and Caspase-9, and down-regulating Bcl-2 in HCC cells both in vitro and in vivo. In addition, AB23A inhibited cell invasion and migration through down-regulating MMP-2/-9 activities. The effects of AB23A might be associated with the PI3K/Akt signaling pathway in HCC cells. Taken together, the present data demonstrated that AB23A might play a role in suppressing the progression of HCC, revealing the value of AB23A for hepatocellular carcinoma treatment in clinic.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cholestenones; Humans; Liver Neoplasms; Phosphatidylinositol 3-Kinases; Signal Transduction; Xenograft Model Antitumor Assays