The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells | |
Lu J.-J.![]() | |
2011-12-01 | |
Source Publication | Investigational New Drugs
![]() |
ISSN | 01676997 15730646 |
Volume | 29Issue: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. |
Keyword | 2-de Dihydroartemisinin Er Stress Gadd153 Grp78 |
DOI | 10.1007/s10637-010-9481-8 |
URL | View the original |
Indexed By | SCI |
WOS Research Area | Oncology ; Pharmacology & Pharmacy |
WOS Subject | Oncology ; Pharmacology & Pharmacy |
WOS ID | WOS:000294824200016 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Institute of Chinese Medical Sciences |
Affiliation | Shanghai 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. |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment