Journal of Medicinal Chemistry
ARTICLE
subconfluent cells in a 10 cm culture dish were co-transfected
with lentiviral vector (10 μg) and the lentiviral packaging vectors
pRSV-REV (2 μg), pMDLg/pRRE (5 μg), and the vesicular stomatitis
virus G glycoprotein (VSVG) expression vector pMD2G (3 μg). The
viruses were collected from the culture supernatants on days 2 and 3
after transfection, concentrated by ultracentrifugation for 1.5 h at
25 000 rpm, and resuspended in PBS. Titers were determined by
infecting H460 cells with serial dilutions of concentrated lentivirus
and counting EGFP-expressing cells after 48 h under a fluorescent
microscope.
4.9. In Vivo Antitumor Study. All animal experiments complied
with the Wenzhou Medical College Policy on the Care and Use of
Laboratory Animals. Five-week-old to 6-week-old athymic BALB/cA
nu/nu female mice (18ꢀ24 g) were purchased from Animal Center of
China Pharmaceutical University (Nanjing, China). Animals were
housed at a constant room temperature with a 12 h:12 h light/dark
cycle and fed a standard rodent diet and water. H460 cells were
harvested and injected subcutaneously into the right flank (3 ꢁ 106
cells in 100 μL of PBS) of 7-week-old female BALB/cA nude mice.
When tumors reach a volume of of 100ꢀ300 mm3 on all mice on day 10,
treated mice were intraperitoneally (ip) injected with a water-soluble
preparation of compound 19 in PBS at a dosage of 10 or 50 mg/kg,
whereas control mice were injected with liposome vehicle in PBS. The
tumor volumes were determined by measuring length (l) and width (w)
and calculating volume (V = lw2/2) as described elsewhere.41
4.10. Statistical Methods. Student’s t test was employed to
analyze the differences between sets of data. Statistics were performed
using GraphPad Pro (GraphPad, San Diego, CA). A p < 0.05 was
considered significant.
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S
Supporting Information. Results from safety assessment
b
of 19 in vivo. This material is available free of charge via the
’ AUTHOR INFORMATION
Corresponding Author
*Phone: (þ86)-577-86699892. Fax: (þ86)-577-86689983.
E-mail: cuiliang1234@163.com.
(13) Scott, D. W.; Loo, G. Curcumin-induced GADD153 upregula-
tion: modulation by glutathione. J. Cell. Biochem. 2007, 101 (2),
307–320.
Author Contributions
^These authors contributed equally to this paper.
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Bredesen, D. E.; Rao, R. V. Coupling endoplasmic reticulum stress to
the cell death program in mouse melanoma cells: effect of curcumin.
Apoptosis 2008, 13 (7), 904–914.
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induced cell cycle arrest and apoptosis in human lung carcinoma A-549
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’ ACKNOWLEDGMENT
The work was supported by grants from the National Natural
Science Foundation of China (Grants 20802054, 30872308, and
30901819), Young Talent Funding of Zhejiang Department of
Health (Grant 2009QN020), Key Project of Wenzhou Science
and Technology Bureau (Grants Y20090009 and Y20100006),
and Zhejiang Natural Science Fund (Grants Y2090358,
Y2090680, Y2090668, and Y4090261).
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small cell lung cancer. Lung Cancer 2010, 67 (3), 257–274.
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’ ABBREVIATIONS USED
ER, endoplasmic reticulum; UPR, unfolded protein response;
CHOP/GADD153, C/EBP-homologous protein/growth arrest
and DNA damage-inducible gene 153; GRP78, glucose-regulate
protein 78; ATF-4, activating transcription factor 4; XBP-1,
X-box binding proteins 1
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dx.doi.org/10.1021/jm200017g |J. Med. Chem. 2011, 54, 3768–3778