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The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells
Lu J.-J.; Chen S.-M.; Zhang X.-W.; Ding J.; Meng L.-H.
2011-12-01
Source PublicationInvestigational New Drugs
ISSN01676997 15730646
Volume29Issue:6Pages:1276-1283
Abstract

Dihydroartemisinin (DHA), the main active metabolite of artemisinin derivatives, is among the artemisinin derivatives possessing potent anti-malarial and anticancer activities. In the present study, we found that DHA displayed significant anti-proliferative activity in human colorectal carcinoma HCT116 cells, which may be attributed to its induction of G1 phase arrest and apoptosis. To further elucidate the mechanism of action of DHA, a proteomic study employed two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed. Glucose-regulated protein 78(GRP78), which is related with endoplasmic reticulum stress (ER stress), was identified to be significantly up-regulated after DHA treatment. Further study demonstrated that DHA enhanced expression of GRP78 as well as growth arrest and DNAdamageinducible gene 153 (GADD153, another ER stress-associated molecule) at both mRNA and protein levels. DHA treatment also led to accumulation of GADD153 in cell nucleus. Moreover, pretreatment of HCT116 cells with the iron chelator deferoxamine mesylate salt (DFO) abrogated induction of GRP78 and GADD153 upon DHA treatment, indicating iron is required for DHA-induced ER stress. This result is consistent with the fact that the antiproliferative activity of DHA is also mediated by iron. We thus suggest the unbalance of redox may result in DHAinduced ER stress, which may contribute, at least in part, to its anti-cancer activity. © Springer Science+Business Media, LLC 2010.

Keyword2-de Dihydroartemisinin Er Stress Gadd153 Grp78
DOI10.1007/s10637-010-9481-8
URLView the original
Indexed BySCI
WOS Research AreaOncology ; Pharmacology & Pharmacy
WOS SubjectOncology ; Pharmacology & Pharmacy
WOS IDWOS:000294824200016
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Cited Times [WOS]:58   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationShanghai Institute of Materia Medica, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Lu J.-J.,Chen S.-M.,Zhang X.-W.,et al. The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells[J]. Investigational New Drugs,2011,29(6):1276-1283.
APA Lu J.-J.,Chen S.-M.,Zhang X.-W.,Ding J.,&Meng L.-H..(2011).The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells.Investigational New Drugs,29(6),1276-1283.
MLA Lu J.-J.,et al."The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells".Investigational New Drugs 29.6(2011):1276-1283.
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