Antitumor Effects of Berberine on Gliomas via Inactivation of Caspase-1-Mediated IL-1β and IL-18 Release

Abstract

Gliomas arise in the glial cells of the brain or spine and are the most prevalent and devastating type of brain tumors. Studies of tumor immunology have established the importance of the tumor micro-environment as a driver of oncogenesis. Inflammatory mediators such as IL-1β and IL-18 released by monocytes regulate transcriptional networks that are required for malignant cell growth. Berberine is a natural botanical alkaloid that is widely found in the Berberis species. Although it has been widely used as an anti-diarrheal treatment in North America for several decades, our study is the first to investigate berberine as an anti-tumor agent in glioma cells. In this study, we demonstrate that berberine significantly inhibits inflammatory cytokine Caspase-1 activation via ERK1/2 signaling and subsequent production of IL-1β and IL-18 by glioma cells. Moreover, we found that berberine treatment led to decreased motility and subsequently cell death in U251 and U87 cells. In addition, our study is the first to indicate that berberine can reverse the process of epithelial-mesenchymal transition, a marker of tumor invasion. Taken together, our work supports berberine as a putative anti-tumor agent targeting glioma cells.

The effect of berberine chloride and/or its combination with vancomycin on the growth, biofilm formation, and motility of Clostridioides difficile

“…Natural products derived from food and other plant extracts have great antimicrobial potential against multi-drugresistant microorganisms [25]. Berberine is a natural isoquinoline alkaloid that is increasingly drawing attention due to its multiple therapeutic effects, among others, on cancer, diabetes, hyperlipidemia, and cardiovascular diseases [26][27][28][29]. In traditional Chinese medicine, berberine has been widely used to treat bacterial diarrhea and gastroenteritis [30].…”

Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells

“…Moreover, BBR affects apoptosis-related proteins and pathways, which lead to the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Caspase can be activated by BBR on different tumor cells [ 24 – 26 ]. In addition, BBR inhibits the proliferation of various tumor cells by inducing cell cycle arrest in in vitro cell experiments [ 27 – 29 ].…”

Intestinal microbiota: a new force in cancer immunotherapy

“…Th cells regulate the function of the intestinal microbiota via the expression of immunoglobulin A (IgA). Furthermore, the secretion of IgA is regulated by the specific binding of PD-1 on the surface of Th cells to PD-L1 on the surface of B cells multiprotein complex that activates caspase 1 and further releases IL-1β and IL-18 [37]. NLRP6 proteins induce intestinal epithelial inflammatory body formation.…”