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Arctigenin Suppresses Unfolded Protein Response and Sensitizes Glucose Deprivation-Mediated Cytotoxicity of Cancer Cells.
- Source :
- Planta Medica; Jan2011, Vol. 77 Issue 1, p141-145, 5p
- Publication Year :
- 2011
-
Abstract
- The involvement of unfolded protein response (UPR) activation in tumor survival and resistance to chemotherapies suggests a new anticancer strategy targeting UPR pathway. Arctigenin, a natural product, has been recently identified for its antitumor activity with selective toxicity against cancer cells under glucose starvation with unknown mechanism. Here we found that arctigenin specifically blocks the transcriptional induction of two potential anticancer targets, namely glucose-regulated protein-78 (GRP78) and its analog GRP94, under glucose deprivation, but not by tunicamycin. The activation of other UPR pathways, e.g., XBP-1 and ATF4, by glucose deprivation was also suppressed by arctigenin. A further transgene experiment showed that ectopic expression of GRP78 at least partially rescued arctigenin/glucose starvation-mediated cell growth inhibition, suggesting the causal role of UPR suppression in arctigenin-mediated cytotoxicity under glucose starvation. These observations bring a new insight into the mechanism of action of arctigenin and may lead to the design of new anticancer therapeutics. [ABSTRACT FROM AUTHOR]
- Subjects :
- DENATURATION of proteins
GLUCOSE
CANCER cells
GENETIC transcription
GROWTH factors
ANTINEOPLASTIC agents
GLYCOLYSIS
WESTERN immunoblotting
ANALYSIS of variance
APOPTOSIS
CELL culture
CELL physiology
GENE expression
LIGNANS
MEDICINAL plants
RESEARCH funding
T-test (Statistics)
TOXICITY testing
TUMORS
IN vitro studies
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 00320943
- Volume :
- 77
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Planta Medica
- Publication Type :
- Periodical
- Accession number :
- 57802548
- Full Text :
- https://doi.org/10.1055/s-0030-1250179