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Network analysis and mechanisms of action of Chinese herb-related
natural compounds in lung cancer cells
Ying-Ju Lina,b, Wen-Miin Liangc, Chao-Jung Chenb,d, Hsinyi Tsange,f, Jian-Shiun Chiouc, Xiang Liue,
Chi-Fung Chengb,c, Ting-Hsu Linb, Chiu-Chu Liaob, Shao-Mei Huangb, Jianxin Cheng, Fuu-Jen
Tsaia,b,h,*, Te-Mao Lia,*
aSchool of Chinese Medicine, China Medical University, Taichung, Taiwan
bGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical
University Hospital, Taichung, Taiwan
cGraduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung,
Taiwan
dGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
eCenter for Biomedical Informatics and Information Technology, National Cancer Institute, National
Institutes of Health, Gaithersburg, MD, USA
fAttain, LLC, McClean, Virginia, USA
gBeijing University of Chinese Medicine, ChaoYang District, Beijing, China
hDepartment of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan
Ying-Ju Lin, Wen-Miin Liang, and Chao-Jung Chen contributed equally to this work.
*Corresponding authors at: School of Chinese Medicine, China Medical University, Taichung,
Taiwan. Tel.: +886 4 22053366; fax: +886 4 22053366.
E-mail addresses: [email protected] (F.J. Tsai), [email protected] (T.M. Li).
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Supplementary Material
Fig. S1. Ingredient–target network for BM. Green diamonds represent BM ingredients; yellow
marks represent targets; yellow marks with red circles represent lung cancer targets.
Fig. S2. Ingredient-target network for JG. Green diamonds represent JG ingredients; yellow
marks represent targets; yellow marks with red circles represent lung cancer targets.
Fig. S3. Ingredient-target network for MMDT. Green diamonds represent MMDT ingredients;
yellow marks represent targets; yellow marks with red circles represent lung cancer targets.
Fig. S4. Effects of three chemotherapy drugs and 17 natural compounds (ingredients) on the
proliferation of human A549 lung cancer cells. A549 cells were incubated with various
concentrations of compounds (10, 50, and 100 μM, respectively) for 24 h. Cell viability was
determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay.
Cell survival rates were calculated as the ratio of optical density of treated cells at 450 nm (10, 50, or
100 µM for each natural compound) to that of non-treated cells. (A) Effects of 17 natural compounds
and three chemotherapy drugs on the proliferation of human A549 lung cancer cells using cell
viability assay. (B) Ursolic acid and 2-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[6,5-f]chromen-3-
yl]-5-methoxyphenol promoted the cytotoxicity of cisplatin. (C) Ursolic acid, 2-[(3R)-8,8-dimethyl-
3,4-dihydro-2H-pyrano[6,5-f]chromen-3-yl]-5-methoxyphenol and licochalcone A didn’t promoted
the cytotoxicity of paclitaxel. (D) Ursolic acid and 2-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[6,5-
f]chromen-3-yl]-5-methoxyphenol promoted the cytotoxicity of topotecan. Each concentration was
tested in quadruplicate, and data are the mean of three independent experiments.
Fig. S5. Ingenuity Pathway Analysis of three ingredients and their lung cancer targets (red
marks).
Fig. S6. KEGG pathway analysis of three ingredients and their lung cancer targets and
mapping to pathways in cancer (yellow colored nodes represent ingredient-lung cancer
targets).
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Fig. S7. Liquid chromatography-tandem mass spectrometry analysis of three ingredients in the
extract of Gan-Cao (GC; Glycyrrhiza uralensis Fisch., family Leguminosae). (A) Chemical
identification of ursolic acid in GC. (B) Chemical identification of glabridin (2-[(3R)-8,8-dimethyl-
3,4-dihydro-2H-pyrano[6,5-f]chromen-3-yl]-5-methoxyphenol) in GC. (C) Chemical identification
of licochalcone A in GC.
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