1. Introduction
Epidemiological data indicate that Asian people have lower rates of certain cancers, including cancers of the breast, prostate, colon, cardiovascular disease, osteoporosis and postmenopausal symptoms.1,2,3 The fact that the traditional Asian diet is rich in soybean and its products containing isoflavones are considered to be responsible for the health advantage of Asian people. Isoflavones are found in nature by a glycosilated form as a minor constituent of soybeans and other leguminous plants.4 It is generally thought that the glycosides are hard to be absorbed while aglycones are better apparently absorbed.5 The isoflavone glycosides are probably hydrolyzed in part by gastric acid and also undergo enzymatic hydrolysis with B - glucosidase produced by intestinal microflora. Isoflavone aglycones are abundantly distributed in the fermented soy products such as miso, natto and tempeh due to the hydrolysis during fermentation by B - glucosidase produced by Saccharomyces rouxii for miso and Bacillus natto for natto, respectively.6 Basidiomycetes mushroom has been used in folk medicine and useful against cancer due to their polysaccharides such as B - glucan which reported to enhance immune response.7 Some basidiomycetes mushrooms are known to produce B - glucosidase8. It was considered that isoflavone glycosides could be converted by B - glucosidase produced from basidiomycetes during the fermentation.
Angiogenesis, the formation of new capillaries from preexisting blood vessels, is a fundamental process involved in embryoinic development and in pathological conditions such as tumorigenesis, diabetic retinopathy, and wound healing. Tumor growth is dependent on angiogenesis process and it requires new vessel growth.9 Recently, intake of soybean isoflavones, especially genistein which is aglycone form, has been reported to play a role in the prevention of hormone related cancers. Genistein has also been reported to inhibit angiogenesis in vitro and in vivo tumor cell proliferation, and in vivo tumor growth.10, 11, 12, 13 Apoptosis is the generically regulated form of cell death that permits the safe disposal of cells at the point in time when they have fulfilled their biological function. (Afford S, Randhawa S, Apoptosis. Mol Pathol 2000, 53(2):55-63) Among the possible molecular mechanisms are: (a) activation of proteases, as ICE (Il-l beta converting enzyme); (b) calpain is activated in several cells, with PARP (Poly-ADP-ribose polymerase). The p53 gene encodes a transcription factor that contributes to several different cellular activities, including apoptosis, the cellular response to radiation, and the activation of protein as GADD, Bel-2 (represses to apoptosis) and Bax. P53 exerts a role as inductor of apoptosis by transactivating expression of the Bax gene. The p21 is an inhibitor of cyclin-dependent kinase, which is transactivated by p53. During apoptosis, there is an activation of both, c-mye, and the transcription factor NF-kB, which is an important regulator of apoptosis. (Merino JJ, Cordero-Campana MI. Molecular bases of the programmed cell death process: implications of tumor suppressor protein p53 and other proteins in the control of cell cycle. Mechanisms of apoptotic action. Invest Clin 1998;39(4):323-58.
Genistein was reported to induce apoptosis and topoisomerase II-mediated DNA breakage (Salti GI, Grewal S. Mehta RR, Das Gupta TK, Boddie AW Jr., Constantinou AI. Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells. Eur J Cancer 2000 Apr;36(6):796-802). Davis JN, Jucuk O, Sarkar FH. Genistein inhibits NF-kappa B activation in prostate cancer cells. Nutr Cancer 1999;35(2):167-74) and suppression of focal adhesion kinase activity and regulation c-myc function (Brown A, Jolly P, Wei H. Genistein modulates neuroblastoma cell proliferation and differentiation through induction of apoptosis and regulation of tyrosine kinase activity and N-myc expression. Cardinogenesis 1998 Jun;19(6):991-7).
It is expected that the combination of genistein with anti-angiogenesis and polysaccharides of basidiomycetes with anti-tumor activities will be useful for cancer treatment and other related diseases.
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