Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells

Title
Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells
Author(s)
Khanal T[Khanal T]김형균[김형균]최재호[최재호]Do MT[Do MT]공민정강미정노금한여희경[여희경]안영태[안영태]강원구김동현[김동현]정태천정혜광[정혜광]
Keywords
JUN NH2-TERMINAL KINASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; GENIPIN-INDUCED APOPTOSIS; CANCER CELLS; C-JUN; MOLECULAR-MECHANISMS; METABOLISM; PHOSPHORYLATION; ACTIVATION; BAICALIN
Issue Date
201203
Publisher
ELSEVIER IRELAND LTD
Citation
TOXICOLOGY LETTERS, v.209, no.3, pp.246 - 254
Abstract
Intestinal microflora (IM) is able to produce toxic and carcinogenic metabolites and induce more potent cytotoxicity against cells than non-metabolites. This study was performed to investigate the cytotoxic responses of geniposide (GS) and its metabolite and to determine the role of metabolism by IM in GS-induced cytotoxicity. Genipin (GP), a GS metabolite, increased cytotoxic effects in cells, but GS did not. Following GS incubation with IM for metabolic activation, increased cytotoxicity was detected compared to GS. Western blot analysis revealed that the activated GS inhibited Bcl-2 expression with a subsequent increase in Bax expression. Likewise, GS activation by IM stimulated caspase-3 and the production of reactive oxygen species (ROS). In addition, activated GS-induced apoptosis was confirmed by apoptosis and ROS assays; N-acetyl-L-cysteine (NAC) suppressed ROS production and apoptotic cell death. Activated GS induced sustained JNK phosphorylation. Moreover, activated GS-induced cell death was reversed by SP600125. Taken together, these findings suggest that human IM is able to metabolize GS into GP, and the related biological activities induce apoptosis through ROS/JNK signaling. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/29549http://dx.doi.org/10.1016/j.toxlet.2011.12.017
ISSN
0378-4274
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약학대학 > 약학부 > Articles
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