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2015 ; 3
(5
): 657-662
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Realgar quantum dots induce apoptosis and necrosis in HepG2 cells through
endoplasmic reticulum stress
#MMPMID26405541
Qin YU
; Wang H
; Liu ZY
; Liu J
; Wu JZ
Biomed Rep
2015[Sep]; 3
(5
): 657-662
PMID26405541
show ga
Realgar (As(4)S(4)) has been used in traditional Chinese medicines for treatment
of malignancies. However, the poor water solubility of realgar limits its
clinical application. To overcome this problem, realgar quantum dots (RQDs;
5.48±1.09 nm) were prepared by a photoluminescence method. The mean particle size
was characterized by high-resolution transmission electron microscopy and
scanning electron microscopy. Our recent studies revealed that the RQDs were
effective against tumor growth in tumor-bearing mice without producing apparent
toxicity. The present study investigated their anticancer effects and mechanisms
in human hepatocellular carcinoma (HepG2) cells. The HepG2 cells and human normal
liver (L02) cells were used to determine the cytotoxicity of RQDs. The portion of
apoptotic and dead cells were measured by flow cytometry with Annexin
V-fluorescein isothiocyanate/propidium iodide double staining. Apoptosis-related
proteins and genes were examined by western blot analysis and reverse
transcription-quantitative polymerase chain reaction, and the mitochondrial
membrane potential was assayed by confocal microscope with JC-1 as a probe. RQDs
exhibited cytotoxicity in a concentration-dependent manner and HepG2 cells were
more sensitive compared with normal L02 cells. At 15 µg/ml, 20% of the cells were
apoptotic, while 60% of the cells were necrotic at 30 µg/ml. The anti-apoptosis
protein Bcl-2 was dose-dependently decreased, while pro-apoptotic protein Bax was
increased. There was a loss of mitochondrial membrane potential and expression of
the stress genes C/EBP-homologous protein 10 and glucose-regulated protein 78 was
increased by RQDs. RQDs were effective in the inhibition of HepG2 cell
proliferation and this effect was due to induction of apoptosis and necrosis
through endoplasmic reticulum stress.