Berberine Suppressed the Progression of Human Glioma Cells by Inhibiting the TGF-β1/SMAD2/3 Signaling Pathway

Abstract

Background: Previous studies have shown that berberine can inhibit glioma progression, although the underlying molecular mechanisms needed to be explored further. The aim of this study was to evaluate the suppressive effects of berberine on human glioma cells, and identify the underlying signaling pathways. Material and Methods: The cytotoxic effect of different concentrations of berberine against normal human glial cells (HEB) and 4 glioma cell lines was evaluated by the CCK-8 assay. Apoptosis was assayed by flow cytometry. In vitro migration and invasion were analyzed by the wound healing and transwell assays. The expression levels of specific proteins were measured by western blotting and ELISA. Results: Berberine significantly inhibited the proliferation of human glioma U-87 cells, and induced apoptosis in the U-87 and LN229 cells by downregulating Bcl-2, and upregulating Bax and caspase-3. In addition, berberine also inhibited migration and invasion of the glioma cells. Furthermore, berberine exerted its effects on the proliferation, migration, invasion, and apoptosis of glioma cells by inhibiting the TGF-β1/SMAD2/3 signaling pathway, and exogenous TGF-β abrogated the pro-apoptotic and anti-oncogenic effects of berberine. Conclusions: Berberine inhibits glioma progression by targeting the TGF-β1/SMAD2/3 signaling pathway.

Unravelling the Effects of Berberine on Metabolic Activity, Apoptosis and Proliferation of Transformed Cells

“…BBR inhibited the proliferation of human glioma U-87 MG cells and induced apoptosis in the U-87 MG and LN229 cells by downregulating Bcl-2 and upregulating Bax and caspase-3. BBR exerted its effects on the proliferation, migration, invasion, and apoptosis of glioma cells by inhibiting the TGF-β1/SMAD2/3 signaling pathway [83]. Similar results have been reported in another study, showing that BBR reduce cell viability of U-87 MG cells in a concentration-and time-dependent manner, suppressed proliferation, and increased oxidative stress and early apoptosis [88].…”

“…BBR decreased ATP levels and mitochondrial membrane potential in both glioblastoma cell lines, and inhibited PI3K/Akt/mTOR pathway [82]. BBR inhibits glioma cells by inducing endoplasmic reticulum stress, disrupting mitochondrial membrane potential, downregulating ERK1/2 activity, and thus triggering apoptosis [83,84]. BBR and its derivatives are able to cross blood-brain barrier and target mitochondria as determined in a zebrafish model [85].…”

Ursolic acid inhibits glioblastoma through suppressing TGFβ-mediated epithelial-mesenchymal transition (EMT) and angiogenesis

“…Furthermore, growing evidence suggests that blocking the EMT process could be a strategic approach to halt glioblastoma's progression and dissemination. For instance, substances like curcumin, resveratrol, berberine, and sulforaphane have been shown to curtail glioblastoma cell migration and invasion by obstructing the EMT process [ [38] , [39] , [40] ]. Additionally, UA's inhibition of EMT in gastric cancer cells has been documented [ 41 ].…”

Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy

“…Many effects of berberine pharmacology have been demonstrated to be linked to its effect on gut microbiota [ 33 ], but berberine can also affect numerous signaling pathways, including the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-κB, the adenosine monophosphate-activated protein kinase (AMPK), the cyclic-AMP response element-binding protein (CREB), the nuclear factor erythroid 2–related factor 2 (Nrf2), and the mitogen-activated protein kinase (MAPK) pathways, thus acquiring neuroprotective effects [ 34 ]. Recently, it has been reported that berberine can inhibit the TGF-β1/SMAD2/3 signaling pathway, thus suppressing tumor progression in four human glioma cell lines [ 35 ].…”