Cell-specific pattern of berberine pleiotropic effects on different human cell lines

Abstract

The natural alkaloid berberine has several pharmacological properties and recently received attention as a potential anticancer agent. In this work, we investigated the molecular mechanisms underlying the anti-tumor effect of berberine on glioblastoma U343 and pancreatic carcinoma MIA PaCa-2 cells. Human dermal fibroblasts (HDF) were used as non-cancer cells. We show that berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF. Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner. In particular, in HDF it induces cell cycle arrest in G2 and senescence, but not autophagy; in the U343 cells, berberine leads to cell cycle arrest in G2 and induces both senescence and autophagy; in MIA PaCa-2 cells, the alkaloid induces arrest in G1, senescence, autophagy, it increases caspase-3 activity and impairs migration/invasion. As demonstrated by decreased citrate synthase activity, the three cell lines show mitochondrial dysfunction following berberine exposure. Finally, we observed that berberine modulates the expression profile of genes involved in different pathways of tumorigenesis in a cell line-specific manner. These findings have valuable implications for understanding the complex functional interactions between berberine and specific cell types.

Combination of Berberine and Matrine Affects Apoptosis and Cellcycle in Human Cervical Cancer Cells

“…In addition, the decrease in the proportion of S phase cells suggested that cell proliferation was inhibited by the treatments. The data also showed that the berberineñmatrine combination had a more significant effect than either drug alone (34)(35).…”

Berberine: A novel therapeutic strategy for cancer

“…G2/M arrest in U343 cells and G1 arrest in MIA PaCa-2 cells were induced by the treatment with 50 μM BBR for 48 hr. 86 Furthermore, with 24-hr treatment of U266 cells with 40, 80, 120, and 160 μmol/L of BBR, the number of cells in the S phase was decreased and the number of cells in the G2/M phase went clearly higher when compared to the untreated controls. These findings suggested that BBR could inhibit the proliferation of multiple myeloma cells and caused cell cycle arrest.…”

“…These findings, thus, indicated that BBR-induced KB cell death is controlled by both extrinsic and intrinsic mitochondrialmediated apoptotic signaling pathways. 85 Agnarelli et al 86 studied MIA PaCa-2 panceratic adenocarcinoma and U343 glioblastoma cells for 48 hr with 50 μM BBR and found that in U343 cells, the activity of caspase-3 decreased and in MIA PaCa-2 cells increased. Moreover, the utilization of BBR in treating HCT-15 colorectal adenocarcinoma cells enhanced the spliced caspase-3 and Bax expression and substantially reduced the expression of surviving and BCL-2 which ultimately caused apoptosis.…”

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

“…The mode of cell growth inhibition and induction of cell death in cancer cells by berberine has been extensively shown to involve apoptosis. This is largely based on induction of mitochondrial dysfunction as shown by changes in mitochondrial permeability and/or membrane potential (∆ψm) and caspase-dependent cell death [28,35,39,57,61]. As a marker of apoptosis, genes and proteins which are known to induce apoptosis in cancer cells (Bax, Bak, Bad, Apaf-1; Fas, FasL and tumour necrosis factor-α (TNF-α)) are upregulated while those associated with cell survival (Bcl-2 and Bcl-xL, survivin) are suppressed [24,35,40,42,47,49,[55][56][57][58][59]61,63].…”