Bufalin, a component in Chansu, inhibits proliferation and invasion of hepatocellular carcinoma cells

Abstract

BackgroundHepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells.MethodsProliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3β, GSK3β, pβ-catenin, β-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and β-catenin expression levels were also evaluated by immunofluorescence.ResultsBufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3β, MMP-9, and MMP-2, while increasing the levels of GSK3β and E-cadherin and suppressing the nuclear translocation of β-catenin.ConclusionsBufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3β/β-catenin/E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages.

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice

“…Our in vivo results revealed that bufalin was able to decrease MMP-2 and MMP-9 expression levels in a dose-dependent manner, whereas our previous in vitro experiments show that bufalin is able to decrease MMP-2 and MMP-9 expressions in hepatoma cell lines [12]. MMP-2 and MMP-9 are zinc-dependent endopeptidases that play critical roles in cancer progression and metastasis [27].…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…In a EGFR mutant lung cancer cell line, it was proved to reverse HGF-induced EGFR-TKIs resistance by blocking the Met/PI3K/Akt signaling pathway (96). In human hepatoma cell lines HCCLM3 and HepG2, bufalin plays a role in suppressing proliferation, migration, invasion and adhesion of hepatoma cells inhibition of the AKT/ GSK3β/β-catenin/E-cadherin signaling pathway (97). There are a number of research reports on the apoptosis effect of bufalin.…”

Radiosynthesis and pharmacokinetics of [¹⁸F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

“…Preceding findings have revealed that the anticancer activity of bufalin could be attributed to its prevention of cell proliferation, instruction of apoptosis, disturbance of the cell cycle, and modulation of the immune response 7–9. Earlier study of ours revealed that bufalin had convincing anticancer growth and reduced the metastatic potentials in the human hepatocellular carcinoma-transplanted tumor model, and the fundamental mechanism was in part mediated by the signaling pathway of the Akt–GSK3β–β-catenin–E-cadherin 10,11. These results indicated that bufalin might be a purposeful constituent for cancer treatment.…”