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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Agnarelli A,Natali M,Garcia-Gil M,Pesi R,Tozzi MG,Ippolito C,Bernardini N,Vignali R,Batistoni R,Bianucci AM,Marracci S

doi

10.1038/s41598-018-28952-3

subject

Has Abstract

pub_date

2018-07-13 00:00:00

pages

10599

issue

1

issn

2045-2322

pii

10.1038/s41598-018-28952-3

journal_volume

8

pub_type

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