Sıçanlarda, 7,12 Dimetil Benzantrasen ile Oluşturulan Yumuşak Doku Sarkomunda Genisteinin Koruyucu Rolü
Genistein, soya fasülyesinde bulunan biyolojik olarak en aktif izoflavondur. Genisteinin östrojenik,antiöstrojenik, anti kanserojenik ve immun regülatör özellikleri bilinmektedir. Bu çalışmada,genisteinin sıçanlarda kimyasal olarak oluşturulan yumuşak doku sarkomu üzerine etkileriaraştırlmıştır. Bu amaçla, 45 adet Wistar albino ırkı erkek sıçan, her biri 15 hayvan içeren 3 deneygrubuna rastgele ayrılmıştır. (i) Kontrol: Herhangi bir uygulama yapılmayan normal kontrolsıçanlarından oluştu. (ii) DMBA grubu: 7,12 dimetil benzantrasen (susam yağında çözülmüşDMBA, 50 mg/kg i.p.) ile fibroid tümör oluşturulan sıçanlardan oluştu. (iii) DMBA+Genistein grubu:Fibroid tümör oluşturulmak amacıyla DMBA’yı i.p. olarak ikinci gruba benzer şekilde alan ve 20hafta boyunca genistein (400 mg/kg diyet) verilen sıçanlardan oluştu. Genistein takviyesi DMBA ilekıyaslandığında fibroid tümörlerin görülme sıklığını azalttı (P
Protective Role of Genistein on DMBA-induced Soft Tissue Sarcoma in Rats
Genistein is the most bioactive isoflavone of soybean. It has been known with its effects as estrogen, antiestrogen, cancer inhibitor, and immune regulator. In this study, we investigated the effects of genistein on chemically induced soft tissue sarcoma in the rats. Forty-five male Wistar albino rats were randomly allocated to 3 experimental groups containing 15 rats in each. (i) Control: Standard control animals (no treatment). (ii) DMBA: These rats received 7,12- dimethylbenz[a]anthracene (DMBA) (50 mg/kg body weight of DMBA dissolved in sesame oil) i.p. injected to develop fibroid tumor. (iii) DMBA+Genistein: This group received DMBA i.p. similarly as DMBA group to develop fibroid tumor as well as supplemented with genistein (400 mg/kg diet) for 20 weeks of the study duration. Genistein supplementation decreased the incidence of fibroid tumors (P
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- Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008.
CA Cancer J Clin 2008; 58: 71-96.
- Banerjee RA, Bandopadhyay DE, Abilash VG.
Epidemiology, pathology, types and diagnosis of soft
tissue sarcoma: A Research Review. Asian J Pharm Clin
Res 2013; 6: 18-25.
- Dancsok AR, Asleh-Aburaya K, Nielsen TO. Advances in
sarcoma diagnostics and treatment. Oncotarget 2017; 8:
7068-7093.
- Weitz J, Klimstra DS, Cymes K, et al. Management of
primary liver sarcomas. Cancer 2007; 109: 1391-1396.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA
Cancer J Clin 2016; 66: 7-30.
- In GK, Hu JS, Tseng WW. Treatment of advanced,
metastatic soft tissue sarcoma: latest evidence and
clinical considerations. Ther Adv Med Oncol 2017; 9: 533-
550.
- Sharma V, Paliwal R, Janmeda P, Sharma S.
Chemopreventive efficacy of Moringa oleifera pods
against 7, 12-dimethylbenz[a]anthracene induced hepatic
carcinogenesis in mice. Asian Pac J Cancer Prev 2012;
13: 2563-2569.
- Abedin Z, Sen S, Field J. Aldo-keto reductases protect
lung adenocarcinoma cells from the acute toxicity of B [a]
P-7, 8-trans-dihydrodiol. Chem Res Toxicol 2011; 25:
113-121.
- Karabulut AB, Karadag N, Gurocak S, et al. Apricot
attenuates oxidative stress and modulates of Bax, Bcl-2,
caspases, NFκ-B, AP-1, CREB expression of rats bearing
DMBA-induced liver damage and treated with a
combination of radiotherapy. Food Chem Toxicol 2014;
70: 128-133.
- Barnes S, Peterson G, Grubbs C, Setchell K. Potential
role of dietary isoflavones in the prevention of cancer. Adv
Exp Med Biol 1998; 354: 135-147.
- Walter ED. Genistin (an Isoflavone Glucoside) and its
Aglucone, Genistein, from Soybeans. J Am Chem Soc
1941; 63: 3273-3276.
- Yildiz F. Phytoestrogens in Functional Foods. 1st Edition,
Taylor & Francis Ltd, Boca Raton, FL, USA, 2005.
- Hilakivi‐Clarke L, Andrade JE, Helferich W. Is soy
consumption good or bad for the breast? J Nutr 2010;
140: 2326-2334.
- Rimbach G, Weinberg PD, de Pascual-Teresa S, et al.
Sulfation of genistein alters its antioxidant properties and
its effect on platelet aggregation and monocyte and
endothelial function. Biochim Biophys Acta 2004; 1670:
229-237.
- Si H, Liu D. Phytochemical genistein in the regulation of
vascular function: new insights. Curr Med Chem 2007; 14:
2581-2589.
- He FJ, Chen JQ. Consumption of soybean, soy foods, soy
isoflavones and breast cancer incidence: Differences
between Chinese women and women in Western
countries and possible mechanisms. Food Sci Hum Welln
2013; 31: 146-161.
- Akiyama T, Ishida J, Nakagawa S, et al. Genistein, a
specific inhibitor of tyrosine-specific protein kinases. J Biol
Chem 1987; 262: 5592-5595.
- Pavese JM, Farmer RL, Bergan RC. Inhibition of cancer
cell invasion and metastasis by genistein. Cancer
Metastasis Rev 2010; 29: 465-482.
- Dutta S, Kharkar PS, Sahu NU, Khanna A. Molecular
docking prediction and in vitro studies elucidate anticancer
activity of phytoestrogens. Life Sci 2017; 185: 73-
84.
- Yeh CC, Fan Y, Jiang L, et al. Genistein Suppresses
Growth of Human Uterine Sarcoma Cell Lines via Multiple
Mechanisms. Anticancer Res 2015; 35: 3167-3173.
- Onderci M, Sahin K, Sahin N, et al. The effect of genistein
supplementation on performance and antioxidant status of
Japanese quail under heat stress. Arch Anim Nutr 2004;
58: 463-471.
- Sahin K, Tuzcu M, Sahin N, et al. Inhibitory effects of
combination of lycopene and genistein on 7, 12-dimethyl
benz(a)anthracene-induced breast cancer in rats. Nutr
Cancer 2011; 63: 1279-1286.
- Gürocak S, Karabulut AB, Tuzcu M, et al. Combinatorial
effect of zoledronic acid and irradiation on the prevention
of DMBA-induced precancerogenic changes in the
mammary tissues of rats. J Cancer Res Ther 2016; 12:
645-649.
- IBM SPSS. IBM Corp. Released 2012. IBM SPSS
Statistics for Windows, Version 21.0. Armonk, NY: IBM
Corp.
- Fletcher CDM, Unni KK, Mertens F. (Eds.): World Health
Organization. Classification of Tumours. Pathology and
Genetics of Tumours of Soft Tissue and Bone. Lyon.
IARC Press, 2002.
- Dorfman HD, Czerniak B. Bone cancers. Cancer 1995;
75: 203-210.
- Nathan FM, Singh VA, Dhanoa A, Palanisamy UD.
Oxidative stress and antioxidant status in primary bone
and soft tissue sarcoma. BMC Cancer 2011; 11: 382.
- Lee GA, Hwang KA, Choi KC. Roles of dietary
phytoestrogens on the regulation of epithelialmesenchymal
transition in diverse cancer metastasis.
Toxins 2016; 24; 8: 162.
- Pelekanou V, Leclercq G. Recent insights into the effect
of natural and environmental estrogens on mammary
development and carcinogenesis. Int J Dev Biol 2011; 55:
869-878.
- Rodríguez-Landa JF, Cueto-Escobedo J, Puga-Olguín A,
et al. The Phytoestrogen Genistein Produces Similar
Effects as 17β-Estradiol on Anxiety-Like Behavior in Rats
at 12 Weeks after Ovariectomy. Biomed Res Int 2017;
2017: 9073816.
- Liu XX, Sun C, Jin XD, et al. Genistein sensitizes
sarcoma cells in vitro and in vivo by enhancing apoptosis
and by inhibiting DSB repair pathways. J Radiat Res
2016; 57: 227-237.
- Engel N, Adamus A, Schauer N, et al. Synergistic Action
of Genistein and Calcitriol in Immature Osteosarcoma
MG-63 Cells by SGPL1 Up-Regulation. PloS one 2017;
12: e0169742.
- Sundaram MK, Ansari MZ, Mutery AA, et al. Genistein
induces alterations of epigenetic modulatory signatures in
human cervical cancer cells. Anticancer Agents Med
Chem 2017; (in Press).
- Pérez-Matute P, Zulet MA, Martínez JA. Reactive species
and diabetes: counteracting oxidative stress to improve
health. Curr Opin Pharmacol 2009; 9: 771-779.
- Zhang H, Zhao Z, Pang X, et al. MiR-34a/sirtuin-1/foxo3a
is involved in genistein protecting against ox-LDL-induced
oxidative damage in HUVECs. Toxicol Lett 2017; 277:
115-122.
- Saha S, Sadhukhan P, Mahalanobish S, Dutta S, Sil PC.
Ameliorative role of genistein against age dependent
chronic arsenic toxicity in murine brains via the regulation
of oxidative stress and inflammatory signaling cascades. J
Nutr Biochem 2017; 55: 26-40.
- Sahin K, Akdemir F, Tuzcu M, et al. Genistein suppresses
spontaneous oviduct tumorigenesis in quail. Nutr Cancer
2009; 61: 799-806.
- Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted
therapy of cancer by genistein Cancer Lett 2008; 269:
226-242.
- Castro L, Gao X, Moore AB, et al. A high concentration of
genistein induces cell death in human uterine leiomyoma
cells by autophagy. Expert Opin Environ Biol 2016; 5: 1-
19.