Characterization of dihydroartemisinin-resistant colon carcinoma
HCT116/R cell line
Jin-Jian Lu
•
Si-Meng Chen
•
Jian Ding
•
Ling-Hua Meng
Received: 11 June 2011 / Accepted: 9 September 2011 / Published online: 30 September 2011
Ó Springer Science+Business Media, LLC. 2011
Abstract Dihydroartemisinin (DHA) is an important
artemisinin derivative and presents profound anti-tumor
potential. A DHA-resistant cell line named HCT116/R
derived from colon carcinoma cell line HCT116 was
established in our previous study. Herein, we found that
HCT116/R cells were much more resistant to DHA- or
artesunate-induced proliferation inhibition and more tol-
erant to DHA-induced cell cycle arrest and apoptosis
compared with those of the parent HCT116 cells. The
protein levels of P-glycoprotein and MDR-associated pro-
tein 1 and the accumulation of doxorubicin in cells were
similar in both cell lines. Moreover, HCT116/R cells were
still sensitive to camptothecin- and doxorubicin-induced
cell growth inhibition. To further explore the character-
ization of HCT116/R cell line, a proteomic study
employing two-dimensional gel electrophoresis and
matrix-assisted laser desorption/ionization time-of-flight
mass spectrometry was performed. Eight different expres-
sed proteins between the two cell lines were identified
including some heat shock proteins, annexins, etc. This
study not only indicates that exposure to DHA may not
induce a tumor multi-drug-resistant phenotype but also
affords new clues for the further investigation of the anti-
cancer mechanisms of DHA and other artemisinin
derivatives.
Keywords Dihydroartemisinin Á Resistant Á Proteomics Á
Anti-tumor Á HCT116
Abbreviations
ARTs Artemisinin and its derivatives
ART Artesunate
CPT Camptothecin
DHA Dihydroartemisinin
DOX Doxorubicin
HSPs Heat shock proteins
HSP27 Heat shock protein beta-1
IEF Isoelectric focusing
MALDI-TOF MS Matrix-assisted laser desorption/
ionization time-of-flight mass
spectrometry
MDR Multi-drug resistance
MRP1 MDR-associated protein 1
P-gp P-glycoprotein
PI Propidium iodide
SRB Sulforhodamin B
2-DE Two-dimensional gel electrophoresis
Introduction
Artemisinin, the active principle of Chinese medicinal herb
Artemisia annua L., and its derivatives (ARTs) are at
present widely used as effective anti-malarial drugs [1].
J.-J. Lu
College of Life Sciences, Zhejiang Chinese Medical University,
Hangzhou 310053, Zhejiang, People’s Republic of China
J.-J. Lu Á S.-M. Chen Á J. Ding (&) Á L.-H. Meng (&)
Division of Anti-tumor Pharmacology, State Key Laboratory
of Drug Research, Shanghai Institutes of Materia Medica,
Chinese Academy of Science, Shanghai 201203,
People’s Republic of China
e-mail: jding@mail.shcnc.ac.cn
L.-H. Meng
e-mail: lhmeng@mail.shcnc.ac.cn
123
Mol Cell Biochem (2012) 360:329–337
DOI 10.1007/s11010-011-1072-2