TY - JOUR
T1 - Subcellular Localization and Activity of Gambogic Acid
AU - Guizzunti, Gianni
AU - Batova, Ayse
AU - Chantarasriwong, Oraphin
AU - Dakanali, Marianna
AU - Theodorakis, Emmanuel A.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/5
Y1 - 2012/5
N2 - The natural product gambogic acid (GA) has shown significant potential as an anticancer agent as it is able to induce apoptosis in multiple tumor cell lines, including multidrug-resistant cell lines, as well as displaying antitumor activity in animal models. Despite the fact that GA has entered phase I clinical trials, the primary cellular target and mode of action of this compound remain unclear, although many proteins have been shown to be affected by it. By thorough analysis of several cellular organelles, at both the morphological and functional levels, we demonstrate that the primary effect of GA is at the mitochondria. We found that GA induces mitochondrial damage within minutes of incubation at low-micromolar concentrations. Moreover, a fluorescent derivative of GA was able to localize specifically to the mitochondria and was displaced from these organelles after competition with unlabeled GA. These findings indicate that GA directly targets the mitochondria to induce the intrinsic pathway of apoptosis, and thus represents a new member of the mitocans.
AB - The natural product gambogic acid (GA) has shown significant potential as an anticancer agent as it is able to induce apoptosis in multiple tumor cell lines, including multidrug-resistant cell lines, as well as displaying antitumor activity in animal models. Despite the fact that GA has entered phase I clinical trials, the primary cellular target and mode of action of this compound remain unclear, although many proteins have been shown to be affected by it. By thorough analysis of several cellular organelles, at both the morphological and functional levels, we demonstrate that the primary effect of GA is at the mitochondria. We found that GA induces mitochondrial damage within minutes of incubation at low-micromolar concentrations. Moreover, a fluorescent derivative of GA was able to localize specifically to the mitochondria and was displaced from these organelles after competition with unlabeled GA. These findings indicate that GA directly targets the mitochondria to induce the intrinsic pathway of apoptosis, and thus represents a new member of the mitocans.
KW - Apoptosis
KW - Caged Garcinia xanthone
KW - Membranes
KW - Mitocan
KW - Mitochondria
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U2 - 10.1002/cbic.201200065
DO - 10.1002/cbic.201200065
M3 - Article
C2 - 22532297
AN - SCOPUS:84861451018
VL - 13
SP - 1191
EP - 1198
JO - ChemBioChem
JF - ChemBioChem
SN - 1439-4227
IS - 8
ER -