Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
Antrodia cinnamomea is a polyporaceous medicinal and native fungus in Taiwan. In this study, we found that AC-SPS-F3, a sulfated glucan from A. cinnamomea, reduced lung cancer cell viability via inhibition of EGFR and mTOR activity. The co-administration of AC-SPS-F3 and cisplatin synergistically inhibited lung cancer cell viability. We identified AC-SPS-F3 was a sulfated β-(1→4)-D-glucan with two long 1,6-branches in each repeat unit. The FT-IR absorption at 1341 cm-1 and 887 cm-1 confirmed the existence of sulfates. The proposed repeat unit of AC-SPS-F3, including the types of main skeleton and side chains, as well as the position of the minor galactopyranosyl and mannopyranosyl residues, were proposed according to the 1D and 2D NMR spectra, shown as follows: The features for the proposed repeat unit of AC-SPS-F3 included two long β-(1→6)-Glcp branches, a very high ratio of sulfate substitution, and partial 2-O and 4-O substituents evenly distributed on the β-(1→6)-Glcp branches. The present study is first to characterize the highly branched sulfated polysaccharides and elucidates its anti-cancer functions.
Fig. 6(B), Fig.4, table 2, AC-SPS-F3
13C NMR, 1H NMR, gel filtration, HPAEC, Western blotting, HPSEC, statistical analysis, hydrolysis, dialysis, cytotoxicity assay, HMBC, centrifugation, COSY, NOESY, HSC, Saito method
inhibited cell viability by about 50–65% after 48h of treatment (at 400 μg/ml); IC50 649.2μg/ml for A549 cells; IC50 542.4 μg/ml for H1975 cells; inhibits EGFR activity and mTOR in H1975 cells
13C NMR data:
Linkage Residue C1 C2 C3 C4 C5 C6
4,4,4,2 S
4,4,4 bDGlcp 104.0 71.0 76.3 69.5 76.5 62.1
4,4,2 S
4,4,6,6,3 aDGlcp 101.2 69.7 72.6 71.0 72.9 62.1
4,4,6,6,2 S
4,4,6,6,6,6,2,2 S
4,4,6,6,6,6,2 bDGalp 104.3 70.9 74.0 70.2 78.6 62.1
4,4,6,6,6,6,6,6,3 aDGlcp 101.2 69.7 72.6 71.0 72.9 62.1
4,4,6,6,6,6,6,6,2 S
4,4,6,6,6,6,6,6,6,2 S
4,4,6,6,6,6,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
4,4,6,6,6,6,6,6 bDGlcp 104.3 75.0 86.6 76.9 77.0 70.2
4,4,6,6,6,6,6,2 S
4,4,6,6,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
4,4,6,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
4,4,6,6,6,2 S
4,4,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
4,4,6,6 bDGlcp 104.3 75.0 86.6 76.9 77.0 70.2
4,4,6,2 S
4,4,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
4,4 bDGlcp 104.0 70.9 77.1 69.5 76.5 70.2
4,2 S
4 bDGlcp 104.0 71.0 76.3 69.5 76.5 62.1
2 S
6,6,6,3 aDGlcp 101.2 69.7 72.6 71.0 72.9 62.1
6,6,6,2 S
6,6,6,6,6,6,3 aDGlcp 101.2 69.7 72.6 71.0 72.9 62.1
6,6,6,6,6,6,2 S
6,6,6,6,6,6,6,6,2 S
6,6,6,6,6,6,6,6 aDManp 99.3 ? ? ? 74.7 62.1
6,6,6,6,6,6,6,2 S
6,6,6,6,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
6,6,6,6,6,6 bDGlcp 104.3 75.0 86.6 76.9 77.0 70.2
6,6,6,6,6,2 S
6,6,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
6,6,6,6,2 S
6,6,6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
6,6,6 bDGlcp 104.3 75.0 86.6 76.9 77.0 70.2
6,6,2 S
6,6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
6,2 S
6 bDGlcp 104.3 74.5 76.3 76.9 77.0 70.2
bDGlcp 104.0 70.9 77.1 69.5 76.5 70.2
1H NMR data:
Linkage Residue H1 H2 H3 H4 H5 H6
4,4,4,2 S
4,4,4 bDGlcp 4.63 3.31 3.54 3.65 3.64 3.65-3.83
4,4,2 S
4,4,6,6,3 aDGlcp 5.28 3.42 3.76 3.31 3.54 3.65-3.83
4,4,6,6,2 S
4,4,6,6,6,6,2,2 S
4,4,6,6,6,6,2 bDGalp 4.43 3.37 3.43 3.76 3.57 3.65-3.83
4,4,6,6,6,6,6,6,3 aDGlcp 5.28 3.42 3.76 3.31 3.54 3.65-3.83
4,4,6,6,6,6,6,6,2 S
4,4,6,6,6,6,6,6,6,2 S
4,4,6,6,6,6,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
4,4,6,6,6,6,6,6 bDGlcp 4.43 3.31 3.65 3.40 3.42 3.76-4.12
4,4,6,6,6,6,6,2 S
4,4,6,6,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
4,4,6,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
4,4,6,6,6,2 S
4,4,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
4,4,6,6 bDGlcp 4.43 3.31 3.65 3.40 3.42 3.76-4.12
4,4,6,2 S
4,4,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
4,4 bDGlcp 4.63 3.37 3.54 3.65 3.64 3.76-4.12
4,2 S
4 bDGlcp 4.63 3.31 3.54 3.65 3.64 3.65-3.8
2 S
6,6,6,3 aDGlcp 5.28 3.42 3.76 3.31 3.54 3.65-3.83
6,6,6,2 S
6,6,6,6,6,6,3 aDGlcp 5.28 3.42 3.76 3.31 3.54 3.65-3.83
6,6,6,6,6,6,2 S
6,6,6,6,6,6,6,6,2 S
6,6,6,6,6,6,6,6 aDManp 4.87 ? ? ? 3.87 3.65-3.83
6,6,6,6,6,6,6,2 S
6,6,6,6,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
6,6,6,6,6,6 bDGlcp 4.43 3.31 3.65 3.40 3.42 3.76-4.12
6,6,6,6,6,2 S
6,6,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
6,6,6,6,2 S
6,6,6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
6,6,6 bDGlcp 4.43 3.31 3.65 3.40 3.42 3.76-4.12
6,6,2 S
6,6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
6,2 S
6 bDGlcp 4.43 3.23 3.54 3.40 3.42 3.76-4.12
bDGlcp 4.63 3.37 3.54 3.65 3.64 3.76-4.12
1H/13C HSQC data:
Linkage Residue C1/H1 C2/H2 C3/H3 C4/H4 C5/H5 C6/H6
4,4,4,2 S
4,4,4 bDGlcp 104.0/4.63 71.0/3.31 76.3/3.54 69.5/3.65 76.5/3.64 62.1/3.65-3.83
4,4,2 S
4,4,6,6,3 aDGlcp 101.2/5.28 69.7/3.42 72.6/3.76 71.0/3.31 72.9/3.54 62.1/3.65-3.83
4,4,6,6,2 S
4,4,6,6,6,6,2,2 S
4,4,6,6,6,6,2 bDGalp 104.3/4.43 70.9/3.37 74.0/3.43 70.2/3.76 78.6/3.57 62.1/3.65-3.83
4,4,6,6,6,6,6,6,3 aDGlcp 101.2/5.28 69.7/3.42 72.6/3.76 71.0/3.31 72.9/3.54 62.1/3.65-3.83
4,4,6,6,6,6,6,6,2 S
4,4,6,6,6,6,6,6,6,2 S
4,4,6,6,6,6,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4,6,6,6,6,6,6 bDGlcp 104.3/4.43 75.0/3.31 86.6/3.65 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4,6,6,6,6,6,2 S
4,4,6,6,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4,6,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4,6,6,6,2 S
4,4,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4,6,6 bDGlcp 104.3/4.43 75.0/3.31 86.6/3.65 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4,6,2 S
4,4,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
4,4 bDGlcp 104.0/4.63 70.9/3.37 77.1/3.54 69.5/3.65 76.5/3.64 70.2/3.76-4.12
4,2 S
4 bDGlcp 104.0/4.63 71.0/3.31 76.3/3.54 69.5/3.65 76.5/3.64 62.1/3.65-3.8
2 S
6,6,6,3 aDGlcp 101.2/5.28 69.7/3.42 72.6/3.76 71.0/3.31 72.9/3.54 62.1/3.65-3.83
6,6,6,2 S
6,6,6,6,6,6,3 aDGlcp 101.2/5.28 69.7/3.42 72.6/3.76 71.0/3.31 72.9/3.54 62.1/3.65-3.83
6,6,6,6,6,6,2 S
6,6,6,6,6,6,6,6,2 S
6,6,6,6,6,6,6,6 aDManp 99.3/4.87 ?/? ?/? ?/? 74.7/3.87 62.1/3.65-3.83
6,6,6,6,6,6,6,2 S
6,6,6,6,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
6,6,6,6,6,6 bDGlcp 104.3/4.43 75.0/3.31 86.6/3.65 76.9/3.40 77.0/3.42 70.2/3.76-4.12
6,6,6,6,6,2 S
6,6,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
6,6,6,6,2 S
6,6,6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
6,6,6 bDGlcp 104.3/4.43 75.0/3.31 86.6/3.65 76.9/3.40 77.0/3.42 70.2/3.76-4.12
6,6,2 S
6,6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
6,2 S
6 bDGlcp 104.3/4.43 74.5/3.23 76.3/3.54 76.9/3.40 77.0/3.42 70.2/3.76-4.12
bDGlcp 104.0/4.63 70.9/3.37 77.1/3.54 69.5/3.65 76.5/3.64 70.2/3.76-4.12
report error
Found 1 record.
Displayed record 1
(later renamed to: Taiwanofungus camphoratus)
nricm.edu.tw>; Chang CC <chiachang