The isoflavonoid genistein, the aglycone of the heteroside genistin, possesses preventive effect on coronary heart disease and osteoporosis, antioxidant, anthelmintic, antineoplastic and anti-inflammatory properties. Much research has been undertaken regarding the action of genistein on cancer-preventing/treating effects, especially on breast and prostate cancer. The aim of this study was to analyze the effect of this compound in vivo by observing tumor size, metastasis potential and melanization in a mouse model of murine melanoma, employing the B164A5 melanoma cell line and C57BL/6J mice. Genistein decreased the tumor volume and weight by approximately 30%. Non-invasive measurements for both melanin and erythema showed that genistein reduced the quantity of melanin and the degree of erythema in direct proportion to the number of days of treatment. HE analysis diagnosed malignant melanoma in both groups, but no metastasis was recorded in the treated group compared with the liver metastasis in the untreated group after a period of 15 days of experiment at a dose of 15 mg/kg body weight of genistein. Genistein showed beneficial effects regarding tumor size, metastasis potential and melanization in a B16 mouse model of murine melanoma.
BarnesS., PetersonT.G., CowardL. (1995) Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. Journal of Cellular Biochemistry Supplement, 22, 181–187.
2.
WeiH., BowenR., ZhangX., LebwohlM. (1998) Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis in mice. Carcinogen, 19, 1509–1514.
3.
DalaisF.S., EbelingP.R., KotsopoulosD., McGrathB.P., TeedeH.J. (2003) The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clinical Endocrinology, 58, 704–709.
4.
NeelakandanC., ChangT., AlexanderT., DefineL., Evancho-ChapmanM., KyuT. (2011) In vitro evaluation of antioxidant and anti-inflammatory properties of genistein-modified hemodialysis membranes. Biomacromolecules, 12, 2447–2455.
5.
GottsteinN., EwinsB.A., EcclestonC., HubbardG.P., KavanaghI.C., MinihaneA.M., WeinbergP.D., RimbachG. (2003) Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function. British Journal of Nutrition, 89, 607–615.
6.
AkiyamaT., IshidaJ., NakagawaS., OgawaraH., WatanabeS., ItohN., ShibuyaM., FukamiY. (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry, 262, 5592–5595.
7.
PolkowskiK., MazurekA.P. (2000) Biological properties of genistein. A review of in vitro and in vivo data. Acta Poloniae Pharmaceutica, 57, 135–155.
8.
SchmidtF., KnobbeC.B., FrankB., WolburgH., WellerM. (2008) The topoisomerase II inhibitor, genistein, induces G2/M arrest and apoptosis in human malignant glioma cell lines. Oncology Reports, 19, 1061–1066.
9.
MakishimaM., HonmaY., SampiK., HattoriM., UmezawaK., MotoyoshiK. (1991) Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells. Leukemia Research, 15, 701–708.
10.
YazakiK. (2006) ABC transporters involved in the transport of plant secondary metabolites. FEBS Letters, 580, 1183–1191.
11.
DaveB., EasonR.R., TillS.R., GengY., VelardeM.C., BadgerT.M., SimmenR.C.M. (2005) The soy isoflavone genistein promotes apoptosis in mammary epithelial cells by inducing the tumor suppressor PTEN. Carcinogen, 26, 1793–1803.
12.
BaxaD.M., LuoX., YoshimuraF.K. (2002) Genistein induces apoptosis in T lymphoma cells via mitochondrial damage. Nutrition and Cancer, 51, 93–101.
13.
LiY., SarkarF.H. (2002) Inhibition of nuclear factor κb activation in pc3 cells by genistein is mediated via akt signaling pathway. Clinical Cancer Research, 8, 2369–2377.
14.
Dahlman-WrightK., CavaillesV., FuquaS.A., JordanV.C., KatzenellenbogenJ.A., KorachK.S., MaggiA., MuramatsuM., ParkerM.G., GustafssonJ.A. (2006) International union of pharmacology LXIV. Estrogen receptors. Pharmacological Reviews, 58, 773–781.
WallaceJ.L., FoyD., YousufH., WarnockM., GowI.F. (2012) The effect of 17β oestradiol, resveratrol, and genistein on Na+/H+ exchange in breast cancer cells lines. Proceedings of the Nutrition Society, 71: (OCE1), E10,doi:10.1017/S0029665112000389.
17.
UllahM.F., AhmadA., ZubairH., KhanH.Y., WangZ., SarkarF.H., HaidS.M. (2011) Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species. Molecular Nutrition & Food Research, 55, 553–559.
18.
MerchantK., Kumi-DiakaJ., RathinaveluA., EsiobuN., ZoellerR., HartmannJ., JohnsonM. (2011) Molecular basis of the anti-cancer effects of genisteinisoflavone in LNCaP prostate cancer cells. Functional Foods in Health and Disease, 1, 91–105.
19.
ShaoM.Z., WuJ., ShenZ.Z., BarskyS.H. (1998) Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Research, 58, 4851–4857.
20.
DiakaJ.K. (2002) Chemosensitivity of human prostate cancer cells PC3 and LNCaP to genistein isoflavone and β-lapachone. Biology of the Cell., 94, 37–44.
21.
RecordI.R., BroadbentJ.L., KingR.A., DreostiI.E., HeadR.J., TonkinA.L. (1997) Genistein inhibits growth of B16 melanoma cells in vivo and in vitro and promotes differentiation in vitro.International Journal of Cancer, 72, 860–864.
22.
TeicherB.A. (2002) Tumor models in cancer research, In B16 Murine Melanoma.AlvarezE. (Ed.), Humana press Inc, New Jersey, 73–87.
23.
NathansonS.D., HaasG.P., MeadM.J., LeeM. (1986) Spontaneous regional lymph node metastases of three variants of the B16 melanoma: Relationship to primary tumor size and pulmonary metastasis. Journal of Surgical Oncology, 33, 41–45.
24.
CiurleaS.A., TiuleaC., CsanyiE., BerkoS., TomaC.C., DeheleanC., LoghinF. (2010) A pharmatoxicological evaluation of a betulin topical formulation tested on C57BL/6J mouse experimental nevi and skin lesions. Studia Universitatis, 20, 5–9.
25.
YamashitaT., KuwaharaT., GonzálezS., TakahashiM. (2005) Non-invasive visualization of melanin and melanocytes by reflectance-mode confocal microscopy. Journal of Investigative Dermatology., 124, 235–240.
26.
HoshinoT., MatsudaM., YamashitaY., TakeharaM., FukuyaM., MinedaK., MajiD., IhnH., AdachiH., SobueG., FunasakaY., MizushimaT. (2010) Suppression of melanin production by expression of hsp70. The Journal of Biological Chemistry, 285, 13254–13263
27.
MattsP.J., DykesP.J., MarksR. (2007) The distribution of melanin in skin determined in vivo.British Journal of Dermatology, 156, 620–628.
28.
YangC.H., ShenS.C., LeeJ.C., WuP.C., HsuehS.F., LuC.Y., MengC.T., HongH.S., YangL.C. (2004) Seeing the gene therapy: application of gene gun technique to transfect and decolour pigmented rat skin with human agouti signaling protein Cdna. Gene Therapy, 11, 1033–1039.
29.
JangH.S., ChoiH.C., HongR.H., KangS.M. (2008) The effect of genistein on melanin synthesis and in vivo whitening. Korean Journal of Microbiology and Biotechnology, 36, 72–81.
ShyongE.Q., LuY., LazinskyA., SaladiR.N., PhelpsR.G., AustinL.M., LebwohlM., WeiH. (2002) Effects of the 4,5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage. Carcinogen, 23, 317–321.
32.
WeiH., SaladiR., LuY., WangY., PalepS.R., MooreJ., PhelpsR., ShyongE., LebwohlM.G. (2003) Isoflavone genistein: photoprotection and clinical implications in dermatology. Journal of Nutrition, 133, 3811S–3819S.
33.
SunB.S., WhangJ.H., LiuL.L., GongS.L., RedmonH.P. (2007) Taurolidine induces apoptosis of murine melanoma cells in vitro and in vivo by modulation of the Bcl-2 family proteins. Journal of Surgical Oncology, 96, 241–248.
34.
WellsJ.W., CowledC.J., FarzanehF., NobleA. (2008) Combined triggering of dendritic cell receptors results in synergistic activation and potent cytotoxic immunity. Journal of Immunology, 181, 3422–3431.
35.
YanC.H., ChenX.G., LiY., HanR. (1999) Effects of genistein, a soybean-derived isoflavone, on proliferation and differentiation of B16-BL6 mouse melanoma cells. Journal of Asian Natural Product Research, 1, 285–299.
36.
HsuM.Y., ElderD., HerlynM. (2002) Human cell culture, melanoma. In The wistar melanoma (WM) cell lines, Volume 1, 259–274.
37.
Fukunaga-KalabisM., MartinezG., TelsonS.M., LiuZ.J., BalintK., JuhaszI., ElderD.E., PerbalB., HerlynM. (2008) Downregulation of CCN3 expression as a potential mechanism for melanoma progression. Oncogene, 28, 2552–2560.
38.
WeinbergR. (2007) The Biology of Cancer.Garland Science, New York.
39.
SchlüterK., GassmannP., EnnsA., KorbT., Hemping-BovenkerkA., HölzenJ., HaierJ. (2006) Organ-specific metastatic tumor cell adhesion and extravasation of colon carcinoma cells with different metastatic potential. American Journal of Pathology, 169, 1064–1073.
40.
GuoT.L., McCayJ.A., ZhangL.X., BrownR.D., YouL., KarrowN.A., GermolecD.R., WhiteK.L. (2001) Genistein modulates immune responses and increases host resistance to b16f10 tumor in adult female b6c3f1 mice. Journal of Nutrition, 131, 3251–3258.
41.
DonghuaL., JohnA.Y., MichaelH.M., PatriciaA., MurphyL.Y. (1999) Soybean isoflavones reduce experimental metastasis in mice. Journal of Nutrition., 129, 1075–1078.
