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Winter 2004,Vol.2,No.1
Ganoderma lucidum
inhibits invasivenessofbreast cancer cells
Veronika Slivova,BS;Tatiana Valachovicova,BS;Jiahua Jiang,PhD;Daniel Sliva,PhD
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ABSTRACT
Ganoderma lucidum
(Reishi) is a popular Asian medical mushroom, which has been widely used in traditional Chinese medicine to treat a variety of diseases. Althoughoriginally used as a mushroom for longevity, the dried pow- der of
Ganoderma lucidum
was recommended as a cancer chemotherapy agent in ancient China. Recent in vitro and animal studies have suggested that
Ganoderma lucidum
exhibits anticancer activity, mainly through stimulation of the host immune system by polysaccharides or by the cyto- toxic effects of triterpenes. We have demonstrated that puri- fied spores or fruiting body of
Ganoderma lucidum
down-regulated the expression of urokinase plasminogenactivator (uPA) and uPA receptor (uPAR), which resulted inthe suppression of cell motility in cancer cells. In this study,we investigated how
Ganoderma lucidum
, in the form of a dietary supplement, can modulate the metastatic behavior of the highly invasive human breast cancer cells MDA-MB-231.Our data demonstrate that
Ganoderma lucidum
inhibits cell adhesion, cell migration, and cell invasion of highly metastat- ic breast cancer cells. Furthermore,
Ganoderma lucidum
suppressed the anchorage-independent growth (colony for- mation) of MDA-MB-231 cells. Based on these results,
Ganoderma lucidum
may contribute to reducing invasionand metastasis of breast cancers by inhibiting cancer cell adhesion, cell migration, cell invasion, and growth of cancer cells.Key words:
Ganoderma lucidum
, breast cancer, adhe- sion, migration, invasion, anchorage-independent growth
INTRODUCTION
Breast cancer is the most common malignancy in womenin the United States,accounting for about 33 percent ofallcancers diagnosed in females.
1
The typical treatment for breast cancer is surgery and/or adjuvant therapy.
2
However, breast cancer often progresses from the nonmetastatic andtherapy-responsive phenotype to the highly invasive andmetastatic phenotype,which is usually resistant to the stan-dard therapeutic procedures.Therefore,breast cancer is thesecond leading cause ofcancer death in the United States,and death usually results from invasion and metastasis.
2
Cancer metastases and invasion are complex,interrelatedprocesses,consisting ofcell adhesion,proteolytic degrada-tion,and cell migration,allowing the spread and colonizationofcancer cells in distant sites ofthe body.
3
Furthermore,can-cer cells can also metastasize by an additional mechanism(anchorage-independent growth),which does not requireintegrin-mediated adhesion.
4
Thus,the inhibition ofeither cell adhesion,migration,invasion,or anchorage-independentgrowth could suppress the potential for breast cancer cells tometastasize.
Ganoderma lucidum
(Reishi),a medical mushroom,has been used as a home remedy for numerous types ofchronic dis-eases.
5
Many bioactive components isolated from
Ganoderma lucidum
have been demonstrated to possess antioxidative,antihypertensive,and anticancer effects.
6-9
Polysaccharides,mainly with the structure of
b
-D-glucans,exert anticancer effects against leukemic cells,
10
and some triterpenes also ex-hibit cytotoxic activity against sarcoma and lung carcinomacells in vitro.
11
On the molecular level,we have recently report-edthat
Ganoderma lucidum
suppresses constitutively activetranscription factors AP-1 and NF-
kb
,which results in thedown-regulation ofurokinase plasminogen activator (uPA)and uPA receptor (uPAR) expression in highly invasive human breast and prostate cancer cells.
12
Furthermore,we haveshownthat spores or fruiting body of
Ganoderma lucidum
inhibitcell motility in both breast and prostate cancer cells.
12
Althoughthe uPA/uPAR system was originally recognized for its pro-teolytic activity (breaking down the extracellular matrix pro-teins),which is necessary for cell invasion,uPA/uPAR is alsoresponsible for cell adhesion and cell migration.
13
The present study was undertaken to further characterizethe effect of
Ganoderma lucidum
on the behavior ofhighly
JOURNALOFCANCERINTEGRATIVEMEDICINE,WINTER 2004,VOL.2,NO.1
25
Ganoderma lucidum
inhibits invasivenessofbreast cancer cells
Veronika Slivova,BS;Tatiana Valachovicova,BS;Jiahua Jiang,PhD;Daniel Sliva,PhD
Cancer Research Laboratory, Methodist Research Institute (VS, TV, JJ, DS); Departmentof Medicine, School of Medicine, Indiana University (DS), Indianapolis, Indiana.
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