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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2013

Open Access 01-12-2013 | Research article

Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

Authors: Tae Gen Son, Eun Ji Gong, Min Ji Bae, Sung Dae Kim, Kyu Heo, Changjong Moon, Kwangmo Yang, Joong Sun Kim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2013

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Abstract

Background

Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes.

Methods

Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred.

Results

Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group.

Conclusion

Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients.
Appendix
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Literature
1.
Babb RR: Radiation proctitis: a review. Am J Gastroenterol. 1996, 91 (7): 1309-1311.PubMed
2.
Szabo S, Sandor Z, Vincze A, Gombos Z, Mohiuddin A, Viravathana T: Radiation-induced enterocolitis: basic and applied science. Eur J Surg Suppl. 1998, 582 (582): 85-89.PubMed
3.
Vigneulle RM, Rao S, Fasano A, MacVittie TJ: Structural and functional alterations of the gastrointestinal tract following radiation-induced injury in the rhesus monkey. Dig Dis Sci. 2002, 47 (7): 1480-1491. 10.1023/A:1015846514471.CrossRefPubMed
4.
Jagetia GC: Radioprotective potential of plants and herbs against the effects of ionizing radiation. J Clin Biochem Nutr. 2007, 40 (2): 74-81. 10.3164/jcbn.40.74.CrossRef
5.
Moon C, Kim SH, Kim JC, Hyun JW, Lee NH, Park JW, Shin T: Protective effect of phlorotannin components phloroglucinol and eckol on radiation-induced intestinal injury in mice. Phytother Res. 2008, 22 (2): 238-242. 10.1002/ptr.2298.CrossRefPubMed
6.
Kim SH, Lee HJ, Kim JS, Moon C, Kim JC, Park HR, Jung U, Jang JS, Jo SK: Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice. J Med Food. 2009, 12 (6): 1353-1358. 10.1089/jmf.2008.1322.CrossRefPubMed
7.
Kim JS, Ryoo SB, Heo K, Kim JG, Son TG, Moon C, Yang K: Attenuating effects of Granulocyte-colony stimulating factor (G-CSF) in radiation induced intestinal injury in mice. Food Chem Toxicol. 2012, 50 (9): 3174-3180. 10.1016/j.fct.2012.05.059.CrossRefPubMed
8.
Kim JS, Heo K, Yi JM, Gong EJ, Yang K, Moon C, Kim SH: Genistein mitigates radiation-induced testicular injury. Phytother Res. 2012, 26 (8): 1119-1125. 10.1002/ptr.3689.CrossRefPubMed
9.
Kruk I, Aboul-Enein HY, Michalska T, Lichszteld K, Kladna A: Scavenging of reactive oxygen species by the plant phenols genistein and oleuropein. Luminescence. 2005, 20 (2): 81-89. 10.1002/bio.808.CrossRefPubMed
10.
Filipe P, Silva JN, Haigle J, Freitas JP, Fernandes A, Santus R, Morliere P: Contrasting action of flavonoids on phototoxic effects induced in human skin fibroblasts by UVA alone or UVA plus cyamemazine, a phototoxic neuroleptic. Photochem Photobiol Sci. 2005, 4 (5): 420-428. 10.1039/b416811a.CrossRefPubMed
11.
Landauer MR, Srinivasan V, Seed TM: Genistein treatment protects mice from ionizing radiation injury. J Appl Toxicol. 2003, 23 (6): 379-385. 10.1002/jat.904.CrossRefPubMed
12.
Zhou Y, Mi MT: Genistein stimulates hematopoiesis and increases survival in irradiated mice. J Radiat Res. 2005, 46 (4): 425-433. 10.1269/jrr.46.425.CrossRefPubMed
13.
Davis TA, Mungunsukh O, Zins S, Day RM, Landauer MR: Genistein induces radioprotection by hematopoietic stem cell quiescence. Int J Radiat Biol. 2008, 84 (9): 713-726. 10.1080/09553000802317778.CrossRefPubMed
14.
Day RM, Barshishat-Kupper M, Mog SR, McCart EA, Prasanna PG, Davis TA, Landauer MR: Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation. J Radiat Res. 2008, 49 (4): 361-372. 10.1269/jrr.07121.CrossRefPubMedPubMedCentral
15.
Hillman GG, Singh-Gupta V, Runyan L, Yunker CK, Rakowski JT, Sarkar FH, Miller S, Gadgeel SM, Sethi S, Joiner MC, Konski AA: Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. Radiother Oncol. 2011, 101 (2): 329-336. 10.1016/j.radonc.2011.10.020.CrossRefPubMedPubMedCentral
16.
Polkowski K, Mazurek AP: Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol Pharm. 2000, 57 (2): 135-155.PubMed
17.
Sarkar FH, Li Y: Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev. 2002, 21 (3–4): 265-280.CrossRefPubMed
18.
Hillman GG, Wang Y, Kucuk O, Che M, Doerge DR, Yudelev M, Joiner MC, Marples B, Forman JD, Sarkar FH: Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model. Mol Cancer Ther. 2004, 3 (10): 1271-1279.PubMed
19.
Hillman GG, Wang Y, Che M, Raffoul JJ, Yudelev M, Kucuk O, Sarkar FH: Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model. BMC Cancer. 2007, 7: 4-10.1186/1471-2407-7-4.CrossRefPubMedPubMedCentral
20.
Raffoul JJ, Wang Y, Kucuk O, Forman JD, Sarkar FH, Hillman GG: Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest. BMC Cancer. 2006, 6: 107-10.1186/1471-2407-6-107.CrossRefPubMedPubMedCentral
21.
Lee HJ, Kim JS, Moon C, Kim JC, Jo SK, Kim SH: Relative biological effectiveness of fast neutrons in a multiorgan assay for apoptosis in mouse. Environ Toxicol. 2008, 23 (2): 233-239. 10.1002/tox.20328.CrossRefPubMed
22.
Holt PR, Moss SF, Kapetanakis AM, Petrotos A, Wang S: Is Ki-67 a better proliferative marker in the colon than proliferating cell nuclear antigen?. Cancer Epidemiol Biomarkers Prev. 1997, 6 (2): 131-135.PubMed
23.
Booth C, Booth D, Williamson S, Demchyshyn LL, Potten CS: Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage. Cell Prolif. 2004, 37 (6): 385-400. 10.1111/j.1365-2184.2004.00320.x.CrossRefPubMed
24.
Driak D, Osterreicher J, Vavrova J, Rehakova Z, Vilasova Z: Morphological changes of rat jejunum after whole body gamma-irradiation and their impact in biodosimetry. Physiol Res. 2008, 57 (3): 475-479.PubMed
25.
Quastler H: The nature of intestinal radiation death. Radiat Res. 1956, 4 (4): 303-320. 10.2307/3570211.CrossRefPubMed
26.
Gunnlaugsson A, Nilsson P, Kjellén E, Johnsson A: The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay. Radiat Oncol. 2009, 4: 61-10.1186/1748-717X-4-61.CrossRefPubMedPubMedCentral
27.
Arora A, Byrem TM, Nair MG, Strasburg GM: Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys. 2000, 373 (1): 102-109. 10.1006/abbi.1999.1525.CrossRefPubMed
28.
Klein CB, King AA: Genistein genotoxicity: critical considerations of in vitro exposure dose. Toxicol Appl Pharmacol. 2007, 224 (1): 1-11. 10.1016/j.taap.2007.06.022.CrossRefPubMed
29.
Wang HK: The therapeutic potential of flavonoids. Expert Opin Investig Drugs. 2000, 9 (9): 2103-2119. 10.1517/13543784.9.9.2103.CrossRefPubMed
30.
Harnish DC, Albert LM, Leathurby Y, Eckert AM, Ciarletta A, Kasaian M, Keith JC: Beneficial effects of estrogen treatment in the HLA-B27 transgenic rat model of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2004, 286 (1): G118-G125.CrossRefPubMed
31.
Yu HP, Hsieh YC, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH: Mechanism of the nongenomic effects of estrogen on intestinal myeloperoxidase activity following trauma-hemorrhage: up-regulation of the PI-3K/Akt pathway. J Leukoc Biol. 2007, 82 (3): 774-780. 10.1189/jlb.0307182.CrossRefPubMed
32.
Singh VK, Grace MB, Parekh VI, Whitnall MH, Landauer MR: Effects of genistein administration on cytokine induction in whole-body gamma irradiated mice. Int Immunopharmacol. 2009, 9 (12): 1401-1410. 10.1016/j.intimp.2009.08.012.CrossRefPubMed
33.
Grace MB, Singh VK, Rhee JG, Jackson WE, Kao TC, Whitnall MH: 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis. J Radiat Res. 2012, 53 (6): 840-853. 10.1093/jrr/rrs060.CrossRefPubMedPubMedCentral
34.
Singh-Gupta V, Zhang H, Banerjee S, Kong D, Raffoul JJ, Sarkar FH, Hillman GG: Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy isoflavones in prostate cancer cells. Int J Cancer. 2009, 124 (7): 1675-1684. 10.1002/ijc.24015.CrossRefPubMedPubMedCentral
35.
Kim JS, Yang M, Jang H, Oui H, Kim SH, Shin T, Jang WS, Lee SS, Moon C: Granulocyte-colony stimulating factor ameliorates irradiation-induced suppression of hippocampal neurogenesis in adult mice. Neurosci Lett. 2010, 486 (1): 43-46. 10.1016/j.neulet.2010.09.041.CrossRefPubMed
36.
Kim J, Lee S, Jeon B, Jang W, Moon C, Kim S: Protection of spermatogenesis against gamma ray-induced damage by granulocyte colony-stimulating factor in mice. Andrologia. 2011, 43 (2): 87-93. 10.1111/j.1439-0272.2009.01023.x.CrossRefPubMed
37.
Li M, Zhang Z, Hill DL, Chen X, Wang H, Zhang R: Genistein, a dietary isoflavone, down-regulates the MDM2 oncogene at both transcriptional and posttranslational levels. Cancer Res. 2005, 65 (18): 8200-8208. 10.1158/0008-5472.CAN-05-1302.CrossRefPubMed
38.
Fang MZ, Chen D, Sun Y, Jin Z, Christman JK, Yang CS: Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res. 2005, 11 (19 Pt 1): 7033-7041.CrossRefPubMed
39.
40.
Maria-Aggeliki KS, Nikolaos KL, Kyrias GM, Vassilis KE: The potential clinical impact of probiotic treatment for the prevention and/or anti-inflammatory therapeutic effect against radiation induced intestinal mucositis. A review. Recent Pat Inflamm Allergy Drug Discov. 2009, 2 (1): 195-200.CrossRef
Metadata
Title
Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice
Authors
Tae Gen Son
Eun Ji Gong
Min Ji Bae
Sung Dae Kim
Kyu Heo
Changjong Moon
Kwangmo Yang
Joong Sun Kim
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2013
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-13-103

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