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Dietary
curcumin inhibits chemotherapy-induced apoptosis in models of human breast
cancer
Somasundaram
S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ
The
Lineberger Comprehensive Cancer Center, The University of North Carolina at
Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA
Curcumin,
the major component of the spice turmeric, is used as a coloring and flavoring
additive in many foods and has attracted interest because of its
anti-inflammatory and chemopreventive activities.
However, this agent also inhibits the generation of reactive oxygen species (ROS)
and the c-Jun NH(2)-terminal kinase (JNK) pathway, and because many
chemotherapeutic drugs generate ROS and activate JNK in the course of inducing
apoptosis, we considered the possibility that curcumin might antagonize their
antitumor efficacy.
Studies in tissue culture revealed that curcumin inhibited camptothecin-,
mechlorethamine-, and doxorubicin-induced apoptosis of MCF-7, MDA-MB-231, and
BT-474 human breast cancer cells by up to 70%.
Inhibition of programmed cell death was time and concentration dependent, but
occurred after relatively brief 3-h exposures, or at curcumin concentrations of
1 microM that have been documented in Phase I chemoprevention trials.
Under these conditions, curcumin exhibited antioxidant properties and inhibited
both JNK activation and mitochondrial release of cytochrome c in a
concentration-dependent manner.
Using an in vivo model of human breast cancer, dietary supplementation with
curcumin was found to significantly inhibit cyclophosphamide-induced tumor
regression.
Such dietary supplementation was accompanied by a decrease in the activation of
apoptosis by cyclophosphamide, as well as decreased JNK activation.
These findings support the hypothesis that dietary curcumin can inhibit
chemotherapy-induced apoptosis through inhibition of ROS generation and blockade
of JNK function, and suggest that additional studies are needed to determine
whether breast cancer patients undergoing chemotherapy should avoid curcumin
supplementation, and possibly even limit their exposure to curcumin-containing
foods.
PMID:
12097302 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12097302&dopt=Abstract
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