Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells

Authors: Kyoung-Sub Song, Ge Li, Jong-Seok Kim, Kaipeng Jing, Tae-Dong Kim, Jin-Pyo Kim, Seung-Bo Seo, Jae-Kuk Yoo, Hae-Duck Park, Byung-Doo Hwang, Kyu Lim, Wan-Hee Yoon

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

Polysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL.

Methods

The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP) activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model.

Results

PL (125-1000 μg/mL) significantly inhibited cell proliferation and decreased β-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of β-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF) transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in β-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased.

Conclusions

These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/β-catenin signaling in certain colon cancer cells.
Appendix
Available only for authorised users
Literature
1.
Goldberg RM: Advances in the treatment of metastatic colorectal cancer. Oncologist. 2005, 10 (Suppl 3): 40-48.CrossRefPubMed
2.
Song KS, Cho SM, Lee JH, Kim HM, Han SB, Ko KS, Yoo ID: B-lymphocyte-stimulating polysaccharide from mushroom Phellinus linteus. Chem Pharm Bull (Tokyo). 1995, 43 (12): 2105-2108.CrossRef
3.
Kim HM, Han SB, Oh GT, Kim YH, Hong DH, Hong ND, Yoo ID: Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Int J Immunopharmacol. 1996, 18 (5): 295-303. 10.1016/0192-0561(96)00028-8.CrossRefPubMed
4.
Kim GY, Oh YH, Park YM: Acidic polysaccharide isolated from Phellinus linteus induces nitric oxide-mediated tumoricidal activity of macrophages through protein tyrosine kinase and protein kinase C. Biochem Biophys Res Commun. 2003, 309 (2): 399-407. 10.1016/j.bbrc.2003.08.018.CrossRefPubMed
5.
Han SB, Lee CW, Jeon YJ, Hong ND, Yoo ID, Yang KH, Kim HM: The inhibitory effect of polysaccharides isolated from Phellinus linteus on tumor growth and metastasis. Immunopharmacology. 1999, 41 (2): 157-164. 10.1016/S0162-3109(98)00063-0.CrossRefPubMed
6.
Li G, Kim DH, Kim TD, Park BJ, Park HD, Park JI, Na MK, Kim HC, Hong ND, Lim K, Hwang BD, Yoon WH: Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells. Cancer Lett. 2004, 216 (2): 175-181. 10.1016/j.canlet.2004.07.014.CrossRefPubMed
7.
Lee HJ, Lee HJ, Lim ES, Ahn KS, Shim BS, Kim HM, Gong SJ, Kim DK, Kim SH: Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type plasminogen activator. Biol Pharm Bull. 2005, 28 (1): 27-31. 10.1248/bpb.28.27.CrossRefPubMed
8.
Guo J, Zhu T, Collins L, Xiao ZX, Kim SH, Chen CY: Modulation of lung cancer growth arrest and apoptosis by Phellinus Linteus. Mol Carcinog. 2007, 46 (2): 144-154. 10.1002/mc.20275.CrossRefPubMed
9.
Zhu T, Guo J, Collins L, Kelly J, Xiao ZJ, Kim SH, Chen CY: Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells. Br J Cancer. 2007, 96 (4): 583-590. 10.1038/sj.bjc.6603595.CrossRefPubMedPubMedCentral
10.
Tsuji T, Du W, Nishioka T, Chen L, Yamamoto D, Chen CY: Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice. PLoS One. 5 (3): e9885-
11.
Sliva D, Jedinak A, Kawasaki J, Harvey K, Slivova V: Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling. Br J Cancer. 2008, 98 (8): 1348-1356. 10.1038/sj.bjc.6604319.CrossRefPubMedPubMedCentral
12.
Giles RH, van Es JH, Clevers H: Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta. 2003, 1653 (1): 1-24.PubMed
13.
Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X: Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002, 108 (6): 837-847. 10.1016/S0092-8674(02)00685-2.CrossRefPubMed
14.
Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W: Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996, 382 (6592): 638-642. 10.1038/382638a0.CrossRefPubMed
15.
Tetsu O, McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999, 398 (6726): 422-426. 10.1038/18884.CrossRefPubMed
16.
Huang D, Du X: Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination. World J Gastroenterol. 2008, 14 (12): 1823-1827. 10.3748/wjg.14.1823.CrossRefPubMedPubMedCentral
17.
Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, Knuechel R, Kirchner T: Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA. 2001, 98 (18): 10356-10361. 10.1073/pnas.171610498.CrossRefPubMedPubMedCentral
18.
Zhang B, Ougolkov A, Yamashita K, Takahashi Y, Mai M, Minamoto T: beta-Catenin and ras oncogenes detect most human colorectal cancer. Clin Cancer Res. 2003, 9 (8): 3073-3079.PubMed
19.
Wong SC, Lo ES, Lee KC, Chan JK, Hsiao WL: Prognostic and diagnostic significance of beta-catenin nuclear immunostaining in colorectal cancer. Clin Cancer Res. 2004, 10 (4): 1401-1408. 10.1158/1078-0432.CCR-0157-03.CrossRefPubMed
20.
Yoon WH, Jung YJ, Kim TD, Li G, Park BJ, Kim JY, Lee YC, Kim JM, Park JI, Park HD, No ZS, Lim K, Hwang BD, Kim YS: Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by reducing matrix metalloproteinases and angiogenesis. Clin Cancer Res. 2004, 10 (13): 4517-4526. 10.1158/1078-0432.CCR-04-0084.CrossRefPubMed
21.
Yoon WH, Park HD, Lim K, Hwang BD: Effect of O-glycosylated mucin on invasion and metastasis of HM7 human colon cancer cells. Biochem Biophys Res Commun. 1996, 222 (3): 694-699. 10.1006/bbrc.1996.0806.CrossRefPubMed
22.
Kang DW MG, Park do Y, Hong KW, Min do S: Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells. Exp Mol Med. 2010, 42 (8): 555-564. 10.3858/emm.2010.42.8.056.CrossRefPubMedPubMedCentral
23.
Shin SYKYJ, Song KS, Kim NY, Jeong SY, Park JH, Seo KS, Heo JY, Kwon HJ, Park JI, Park SK, Kweon GR, Yoon WH, Hwang BD, Lim K: Mechanism of Anti-invasive action of Docosahexaenoic Acid in SW480 human colon cancer cell. Journal of Life Science. 2010, 20 (4): 561-571. 10.5352/JLS.2010.20.4.561.CrossRef
24.
Bae DG, Gho YS, Yoon WH, Chae CB: Arginine-rich anti-vascular endothelial growth factor peptides inhibit tumor growth and metastasis by blocking angiogenesis. J Biol Chem. 2000, 275 (18): 13588-13596. 10.1074/jbc.275.18.13588.CrossRefPubMed
25.
Alvarez OA, Carmichael DF, DeClerck YA: Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. J Natl Cancer Inst. 1990, 82 (7): 589-595. 10.1093/jnci/82.7.589.CrossRefPubMed
26.
Eunsook Nam CP: Maspin Suppresses Survival of Lung Cancer Cells through Modulation of Akt Pathway. Cancer Res Treat. 2010, 42 (1): 42-47. 10.4143/crt.2010.42.1.42.CrossRefPubMedPubMedCentral
27.
Clevers H: Wnt/beta-catenin signaling in development and disease. Cell. 2006, 127 (3): 469-480. 10.1016/j.cell.2006.10.018.CrossRefPubMed
28.
Henderson BR: Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover. Nat Cell Biol. 2000, 2 (9): 653-660. 10.1038/35023605.CrossRefPubMed
29.
Munemitsu S, Albert I, Souza B, Rubinfeld B, Polakis P: Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Sci USA. 1995, 92 (7): 3046-3050. 10.1073/pnas.92.7.3046.CrossRefPubMedPubMedCentral
30.
Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 1990, 61 (5): 759-767. 10.1016/0092-8674(90)90186-I.CrossRefPubMed
31.
Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P: Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Carcinogenesis. 2007, 28 (6): 1202-1209. 10.1093/carcin/bgl254.CrossRefPubMed
32.
Ougolkov AV, Yamashita K, Mai M, Minamoto T: Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer. Gastroenterology. 2002, 122 (1): 60-71. 10.1053/gast.2002.30306.CrossRefPubMed
33.
Baldus SE, Monig SP, Huxel S, Landsberg S, Hanisch FG, Engelmann K, Schneider PM, Thiele J, Holscher AH, Dienes HP: MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res. 2004, 10 (8): 2790-2796. 10.1158/1078-0432.CCR-03-0163.CrossRefPubMed
34.
Doyle JL, Haas TL: Differential role of beta-catenin in VEGF and histamine-induced MMP-2 production in microvascular endothelial cells. J Cell Biochem. 2009, 107 (2): 272-283. 10.1002/jcb.22123.CrossRefPubMed
35.
Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T, Yamada Y, Costantini F, Wakisaka S, Pacifici M, Iwamoto M, Enomoto-Iwamoto M: Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem. 2005, 280 (19): 19185-19195. 10.1074/jbc.M414275200.CrossRefPubMed
36.
Brabletz T, Jung A, Dag S, Reu S, Kirchner T: beta-Catenin induces invasive growth by activating matrix metalloproteinases in colorectal carcinoma. Verh Dtsch Ges Pathol. 2000, 84: 175-181.PubMed
37.
Zhai Y, Wu R, Schwartz DR, Darrah D, Reed H, Kolligs FT, Nieman MT, Fearon ER, Cho KR: Role of beta-catenin/T-cell factor-regulated genes in ovarian endometrioid adenocarcinomas. Am J Pathol. 2002, 160 (4): 1229-1238. 10.1016/S0002-9440(10)62550-3.CrossRefPubMedPubMedCentral
38.
Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002, 2 (3): 161-174. 10.1038/nrc745.CrossRefPubMed
39.
Sidenius N, Blasi F: The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy. Cancer Metastasis Rev. 2003, 22 (2-3): 205-222.CrossRefPubMed
40.
Kim GY, Han MG, Song YS, Shin BC, Shin YI, Lee HJ, Moon DO, Lee CM, Kwak JY, Bae YS, Lee JD, Park YM: Proteoglycan isolated from Phellinus linteus induces toll-like receptors 2- and 4-mediated maturation of murine dendritic cells via activation of ERK, p38, and NF-kappaB. Biol Pharm Bull. 2004, 27 (10): 1656-1662. 10.1248/bpb.27.1656.CrossRefPubMed
41.
Park SK, Kim GY, Lim JY, Kwak JY, Bae YS, Lee JD, Oh YH, Ahn SC, Park YM: Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells. Biochem Biophys Res Commun. 2003, 312 (2): 449-458. 10.1016/j.bbrc.2003.10.136.CrossRefPubMed
42.
Han SB, Lee CW, Kang JS, Yoon YD, Lee KH, Lee K, Park SK, Kim HM: Acidic polysaccharide from Phellinus linteus inhibits melanoma cell metastasis by blocking cell adhesion and invasion. Int Immunopharmacol. 2006, 6 (4): 697-702. 10.1016/j.intimp.2005.10.003.CrossRefPubMed
43.
Fidler IJ, Ellis LM: The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell. 1994, 79 (2): 185-188. 10.1016/0092-8674(94)90187-2.CrossRefPubMed
44.
Song YS, Kim SH, Sa JH, Jin C, Lim CJ, Park EH: Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus. J Ethnopharmacol. 2003, 88 (1): 113-116. 10.1016/S0378-8741(03)00178-8.CrossRefPubMed
Metadata
Title
Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells
Authors
Kyoung-Sub Song
Ge Li
Jong-Seok Kim
Kaipeng Jing
Tae-Dong Kim
Jin-Pyo Kim
Seung-Bo Seo
Jae-Kuk Yoo
Hae-Duck Park
Byung-Doo Hwang
Kyu Lim
Wan-Hee Yoon
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-307

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue

Research article

Sociodemographic gradients in breast and cervical cancer screening in Korea: the Korean National Cancer Screening Survey (KNCSS) 2005-2009

Research article

Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

Review

Renal cell cancer among African Americans: an epidemiologic review

Research article

Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Research article

CD248 facilitates tumor growth via its cytoplasmic domain

Research article

Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits