Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction

Ki Seong Eom, Hyung-Jin Kim, Hong-Seob So, Raekil Park, Tae Young Kim
Biological & Pharmaceutical Bulletin 2010, 33 (10): 1644-9
Berberine has a wide range of biochemical and pharmacologic effects, including antitumor activity, but the mechanisms involved in berberine-induced apoptosis remain unclear. The purpose of the present study was to investigate the changes in oxidative stress and endoplasmic reticulum (ER)-related molecules, which are closely associated with cell death-signaling transduction pathways, in human glioblastoma T98G cells treated with berberine. Berberine significantly decreased the cell viability of T98G cells in a dose-dependent manner. Berberine increased the production of reactive oxygen species (ROS) and level of intracellular Ca(2+). Berberine induced ER stress as evidenced by the detection of ER stress-associated molecules such as phosphorylated protein kinase-like ER kinase, eukaryotic translation initiation factor-2α, glucose-regulated protein 78/immunoglobulin heavy chain-binding protein, and CCAAT/enhancer-binding protein (C/EBP)-homologous protein/growth arrest and DNA damage-inducible gene 153, which was associated with the activation of caspase-3. Furthermore, the administration of the antioxidants, N-acetylcysteine and glutathione, reversed berberine-induced apoptosis. Berberine also markedly enhanced apoptosis in T98G cells through the induction of a higher ratio of Bax/Bcl-2 proteins, disruption of the mitochondrial membrane potential, activation of caspase-9 and -3, and cleavage of the poly(ADP-ribose) polymerase (PARP). The inhibition of ER stress using salubrinal led to an increased the level of Bcl-2, whereas the level of Bax, cleavage of procaspase-9 and -3, and PARP were decreased when compared with cells treated with berberine alone, indicating that berberine-induced apoptosis is associated with mitochondrial dysfunction. These results demonstrate that berberine induces apoptosis via ER stress through the elevation of ROS and mitochondrial-dependent pathway in human glioblastoma T98G cells.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"