JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2018, 67(1):3-13 | DOI: 10.36290/csf.2018.001

Genistein: a promising molecule modulating tumour growth and wound healing?

Petra Mitrengová1, Pavel Mučaji1, Vlasta Peržeľová2, Erik Dosedla3, Peter Gál4,5,*
1 Katedra farmakognózie a botaniky, Farmaceutická fakulta, Univerzita Komenského, Bratislava, SR
2 Referát biomedicínskeho výskumu, Východoslovenský ústav srdcových a cievnych chorôb, a.s., Košice, SR
3 Gynekologicko-pôrodnícka klinika, Univerzita Pavla Jozefa Šafárika a Nemocnica Košice-Šaca a.s., 1. súkromná nemocnica, Košice-Šaca, SR
4 Východoslovenský ústav srdcových a cievnych chorôb, a.s., Košice, SR
5 Ústav farmakológie, Lekárska fakulta, Univerzita Pavla Jozefa Šafárika, Košice, SR

Although it has been shown that oestrogen replacement therapy is able to improve wound healing, several side effects of this replacement therapy have precluded its common use in clinical practice. On the other hand, the phytoestrogen genistein (the selective oestrogen receptor modulator belonging to the group of isoflavones) has been introduced into several clinical trials to improve cancer treatment efficiency and experiments suggest its positive effect on wound healing. The main mechanisms of action, which have been elucidated so far, include induction of apoptosis, cell cycle arrest, inhibition of angiogenesis and tyrosine kinase activity as well as cancer chemoprevention and reduction of climacteric symptoms. Unfortunately, all underlying mechanism in the modulation of biological processes involved in wound healing and tumour growth are not yet fully understood. Therefore, the present review summarizes the effects of genistein on biological processes in different wound healing models and selected tumours.

Keywords: genistein; tissue repair and regeneration; carcinoma; skin
Grants and funding:

Táto práca vznikla s podporou Vedeckej grantovej agentúry Ministerstva školstva, vedy, výskumu a športu Slovenskej republiky (VEGA-1/0404/15, VEGA-1/0048/15 a VEGA-1/0561/18), Agentúry na podporu výskumu a vývoja (APVV-14-0731, APVV-16-0446 a APVV-16-0207) a grantu Univerzity Komenského UK/109/2017.

Received: January 4, 2018; Accepted: January 19, 2018; Published: January 1, 2018  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Mitrengová P, Mučaji P, Peržeľová V, Dosedla E, Gál P. Genistein: a promising molecule modulating tumour growth and wound healing? Čes. slov. farm. 2018;67(1):3-13. doi: 10.36290/csf.2018.001.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Ososki A. L., Kennelly E. J. Phytoestrogens: a review of the Present State of Research. Phytother. Res. 2003; 17, 845-869. Go to original source... Go to PubMed...
    2. Brzezinski A., Debi A. Phytoestrogens: the "natural" selective estrogen receptor modulators? Eur J. Obstet. Gynecol. Reprod. Biol. 1999; 85, 47-51. Go to original source... Go to PubMed...
    3. Kelly P. M., Keely N. O., Bright S. A., Yassin B., Ana G., Fayne D., Zisterer D. M., Meegan M. J. Novel selective estrogen receptor ligand conjugates incorporating endoxifen-combretastatin and cyclofenil-combretastatin hybrid scaffolds: Synthesis and biochemical evaluation. Molecules 2017; 22, 1440. Go to original source... Go to PubMed...
    4. Lee I. R., Dawson S. A., Watherall J. D., Hahnel R. Sex hormone-binding globulin secretion by human hepatocarcinoma cells is increased by estrogens and androgens. J. Clin. Endocrinol. Metab. 1987; 64, 825-831. Go to original source... Go to PubMed...
    5. Cassidy A. Potential risks and benefits of phytoestrogen-rich diets. Int. J. Vitam. Nutr. Res. 2003; 73, 120-126. Go to original source... Go to PubMed...
    6. Mezei O., Banz W. J., Steger R. W., Peluso M. R., Winters T. A., Shay N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J. Nutr. 2003; 133, 1238-1243. Go to original source... Go to PubMed...
    7. Chemical Book. © 2016 citované 2017-01-27). Dostupné na: http://www.chemicalbook.com/ChemicalProductProperty_EN_CB6163787.htm
    8. Roland W. S., Vincken J. P., Gouka R. J., van Buren L., Gruppen H., Smit G. Soy Isoflavones and Other Isoflavonoids Activate the Human Bitter Taste Receptors hTAS2R14 and hTAS2R39. J. Agric. Food Chem. 2011; 59, 11764-11771. Go to original source... Go to PubMed...
    9. Yang Z., Kulkarni K., Zhu W., Hu M. Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME. Anticancer Agents Med. Chem. 2012; 12, 1264-1280. Go to original source... Go to PubMed...
    10. Wu J. G., Ge J., Zhang Y. P., Yu Y., Zhang X. Y. Solubility of Genistein in Water, Methanol, Ethanol, Propan-2-ol, 1-Butanol, and Ethyl Acetate from (280 to 333) K. J. Chem. Eng. Data 2010; 55, 5286-5288. Go to original source...
    11. Fukutake M., Takahashi M., Ishida K., Kawamura H., Sugimura T., Wakabayashi K. Quantification of Genistein and Genistin in Soybean and Soybean products. Food Chem. Toxicol. 1996; 34, 457-461. Go to original source... Go to PubMed...
    12. Dalu A., Haskell J. F., Coward L., Lamartiniere C. A. Genistein, a Component of Soy, Inhibits the Expression of the EGF and ErbB2/Neu Receptors in the Rat Dorsolateral Prostate. Prostate. 1998; 37, 36-43. Go to original source...
    13. Banerjee S., Li Y., Wang Z., Sarkar F. H. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008; 269, 226-242. Go to original source... Go to PubMed...
    14. Kim Y. S., Choi K. C., Hwang K. A. Genistein suppressed epithelial-mesenchymal transition and migration efficacies of BG-1 ovarian cancer cells activated by estrogenic chemicals via estrogen receptor pathway and down-regulation of TGF-β signaling pathway. Phytomedicine 2015; 22, 993-999. Go to original source... Go to PubMed...
    15. Kuiper G. G., Lemmen J. G., Carlsson B., Corton J. C., Safe S. H., van der Saag P. T., van der Burg B., Gustafsson J. A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 1998; 139, 4252-4263. Go to original source... Go to PubMed...
    16. Polkowski K., Popiołkiewicz J., Krzeczyński P., Ramza J., Pucko W., Zegrocka-Stendel O., Boryski J., Skierski J. S., Mazurek A. P., Grynkiewicz G. Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines. Cancer Lett. 2004; 203, 59-69. Go to original source... Go to PubMed...
    17. Popiołkiewicz J., Polkowski K., Skierski J.S., Mazurek A. P. In vitro toxicity evaluation in the development of new anticancer drugs - genistein glycosides. Cancer Lett. 2005; 229, 67-75. Go to original source... Go to PubMed...
    18. Kwon S. H., Kang M. J., Huh J. S., Ha K. W., Lee J. R., Lee S. K., Lee B. S., Han I. H., Lee M. S., Lee M. W., Lee J., Choi Y. W. Comparison of oral bioavailability of genistein and genistin in rats. Int. J. Pharm. 2007; 337, 148-154. Go to original source... Go to PubMed...
    19. Steensma A., Faassen-Peters M. A., Noteborn H. P., Rietjens I. M. Bioavailability of Genistein and Its Glycoside Genistin As Measured in the Portal Vein of Freely Moving Unanesthetized Rats. J. Agric. Food Chem. 2006; 54, 8006-8012. Go to original source... Go to PubMed...
    20. Pasqualini J. R. Breast Cancer: Prognosis, Treatment, and Prevention. New York, Basel: CRC Press 2002. Go to original source...
    21. Liu B., Edgerton S., Yang X., Kim A., Ordonez-Ercan D., Mason T., Alvarez K., McKimmey C., Liu N., Thor A. Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Res. 2005; 65, 879-886. Go to original source...
    22. Kapiotis S., Hermann M., Held I., Seelos C., Ehringer H., Gmeiner B. M. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler. Thromb. Vasc. Biol. 1997; 17, 2868-2874. Go to original source... Go to PubMed...
    23. Akiyama T., Ishida J., Nakagawa S., Ogawara H., Watanabe S., Itoh N., Shibuya M., Fukami Y. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Biol. Chem. 1987; 262, 5592-5595. Go to original source...
    24. Stahl S., Chun T. Y., Gray W. G. Phytoestrogens act as estrogen agonists in an estrogen-responsive pituitary cell line. Toxicol. Appl. Pharmacol. 1998; 152, 41-48. Go to original source... Go to PubMed...
    25. Jurzak M., Ramos P., Pilawa B. The influence of genistein on free radicals in normal dermal fibroblasts and keloid fibroblasts examined by EPR spectroscopy. Med. Chem. Res. 2017; 26, 1297-1305. Go to original source... Go to PubMed...
    26. Zhang Z., Wang C. Z., Du G. J., Qi L. W., Calway T., He T. C., Du W., Yuan C. S. Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53- dependent pathway in human colon cancer cells. Int. J. Oncol. 2013; 43, 289-296. Go to original source... Go to PubMed...
    27. Varinská L., Gál P., Mojžišová G., Mirossay L., Mojžiš J. Soy and breast cancer: focus on angiogenesis. Int. J. Mol. Sci. 2015; 16, 11728-11749. Go to original source... Go to PubMed...
    28. Su S. J., Yeh T. M., Chuang W. J., Ho C. L., Chang K. L., Cheng H. L., Liu H. S., Cheng H. L., Hsu P. Y., Chow N. H. The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem. Pharmacol. 2005; 69, 307-318. Go to original source... Go to PubMed...
    29. Guo Y., Wang S., Hoot D. R., Clinton S. K. Suppression of VEGF-mediated autocrine and paracrine interactions between prostate cancer cells and vascular endothelial cells by soy isoflavones. J. Nutr. Biochem. 2007; 18, 408-417. Go to original source... Go to PubMed...
    30. Zhou J. R., Gugger E. T., Tanaka T., Guo Y., Blackburn G. L., Clinton S. K. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J. Nutr. 1999; 129, 1628-1635. Go to original source... Go to PubMed...
    31. Bakkiyanathan A., Joseph A. M., Tharani L., Malathi R. Genistein, the phytoestrogen induces heart-and-soul (has) phenotypes in zebrafish embryo. J. Dev. Biol. Tissue Eng. 2010; 2, 18-22.
    32. Mukhopadhyay S., Ballard B. R., Mukherjee S., Kabir S. M., Das S. K. Beneficial effects of soy protein in the initiation and progression against dimethylbenz(a) anthracene-induced breast tumors in female rats. Mol. Cell Biochem. 2006; 290: 169-176. Go to original source... Go to PubMed...
    33. Farina H. G., Pomies M., Alonso D. F., Gomez D. E. Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol. Rep. 2006; 16, 885-891. Go to original source...
    34. Lamartiniere, C. A. Protection against breast cancer with genistein: a component of soy. Am. J. Clin. Nutr. 2000; 71, 1705-1707. Go to original source... Go to PubMed...
    35. Allred C. D., Allred K. F., Ju Y. H., Virant S. M., Helferich W. G. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. 2001; 61, 5045-5050.
    36. Hsieh C. Y., Santell R. C., Haslam S. Z., Helferich W. G. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1998; 58, 3833-3838.
    37. Chang E. C., Charn T. H., Park S. H., Helferich W. G., Komm B., Katzenellenbogen J. A., Katzenellenbogen B. S. Estrogen receptors α and β as determinants of gene expression: influence of ligand, dose, and chromatin binding. Mol. Endocrinol. 2008; 22, 1032-1043. Go to original source... Go to PubMed...
    38. Li Z., Li J., Mo B., Hu C., Liu H., Qi H., Wang X., Xu J. Genistein induces G2/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells. Cell Biol. Toxicol. 2008; 24, 401-409. Go to original source... Go to PubMed...
    39. Wang T. T. Y., Sathyamoorthy N., Phang J. M. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis 1996; 17, 271-275. Go to original source... Go to PubMed...
    40. Leung L. K., Wang T. T. Bcl-2 is not reduced in the death of MCF-7 cells at low genistein concentration. J. Nutr. 2000; 130, 2922-2926. Go to original source... Go to PubMed...
    41. Pagliacci M. C., Smacchia M., Migliorati G., Grignani F., Riccardi C., Nicoletti I. Growth-inhibitory effects of the natural phytoestrogen genistein in MCF-7 human breast cancer cells. Eur. J. Cancer. 1994; 30, 1675-1682. Go to original source... Go to PubMed...
    42. Paruthiyil S., Parmar H., Kerekatte V., Cunha G. R., Firestone G. L., Leitman D. C. Estrogen receptor β inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Cancer Res. 2004; 64, 423-428. Go to original source... Go to PubMed...
    43. Jiang Y., Gong P., Madak-Erdogan Z., Martin T., Jeyakumar M., Carlson K., Khan I., Smillie T. J., Chittiboyina A. G., Rotte S. C. K., Helferich W. G., Katzenellenbogen J. A., Katzenellenbogen B. S. Mechanisms enforcing the estrogen receptor β selectivity of botanical estrogens. FASEB J. 2013; 27, 4406-4418. Go to original source... Go to PubMed...
    44. Gong L., Li Y., Nedeljkovic-Kurepa A., Sarkar F. H. Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene 2003; 22, 4702-4709. Go to original source... Go to PubMed...
    45. Mai Z., Blackburn G. L., Zhou J. R. Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Mol. Carcinog. 2007; 46, 534-542. Go to original source... Go to PubMed...
    46. Li Y., Ahmed F., Ali S., Philip P. A., Kucuk O., Sarkar F. H. Inactivation of nuclear factor KB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res. 2005; 65, 6934-6942. Go to original source... Go to PubMed...
    47. Seo H. S., DeNardo D. G., Jacquot Y., Laïos I., Vidal D. S., Zambrana C. R., Leclercq G., Brown P. H. Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha. Breast Cancer Res. Treat. 2006; 99, 121-134. Go to original source... Go to PubMed...
    48. Pan H., Zhou W., He W., Liu X., Ding Q., Ling L., Zha X., Wang S. Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int. J. Mol. Med. 2012; 30, 337-343. Go to original source... Go to PubMed...
    49. Shim H. Y., Park J. H., Paik H. D., Nah S. Y., Kim D. S., Han Y. S. Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain-caspase and apoptosis signaling kinase 1-p38 mitogen-activated protein kinase activation Cascades. Anticancer Drugs 2007; 18, 649-657. Go to original source... Go to PubMed...
    50. Prietsch R. F., Monte L. G., da Silva F. A., Beira F. T., Del Pino F. A., Campos V. F., Collares T., Pinto L. S., Spanevello R. M., Gamaro G. D., Braganhol E. Genistein induces apoptosis and autophagy in human breast MCF-7 cells by modulating the expression of proapoptotic factors and oxidative stress enzymes. Mol. Cell. Biochem. 2014; 390, 235-242. Go to original source... Go to PubMed...
    51. Ovarian Cancer Research Fund Alliance © 2016 citované 2017-11-22). Dostupné na: https://ocrfa.org/patients/about-ovarian-cancer/statistics/
    52. Luo H., Jiang B. H., King S. M., Chen Y. C. Inhibition of Cell Growth and VEGF Expression in Ovarian Cancer Cells by Flavonoids. Nutr. Cancer 2008; 60, 800-809. Go to original source... Go to PubMed...
    53. Ouyang G., Yao L., Ruan K., Song G., Mao Y., Bao S. Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways. Cell. Biol. Int. 2009; 33, 1237-1244. Go to original source... Go to PubMed...
    54. Antosiak A., Milowska K., Maczynska K., Rozalska S., Gabryelak T. Cytotoxic activity of genistein-8-C-glucoside form Lupinus luteus L. and genistein against human SK-OV-3 ovarian carcinoma cell line. Med. Chem. Res. 2016; 26, 64-73. Go to original source... Go to PubMed...
    55. American Cancer Society. Colorectal Cancer Facts & Figures 2014-2016. Atlanta: American Cancer Society © 2014 citované 2017-11-23). Dostupné na: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2014-2016.pdf
    56. Raju J., Bielecki A., Caldwell D., Lok E., Taylor M., Kapal K., Curran I., Cooke G. M., Bird R. P., Mehta R. Soy isoflavones modulate azoxymethane-induced rat colon carcinogenesis exposed pre- and postnatally and inhibit growth of DLD-1 human colon adenocarcinoma cells by increasing the expression of estrogen receptor-b 1-3. J. Nutr. 2009; 139, 474-481. Go to original source... Go to PubMed...
    57. Qi W., Weber C. R., Wasland K., Savkovic S. D. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer 2011; 11, 219. Go to original source... Go to PubMed...
    58. Pool-Zobel B. L., Adlercreutz H., Glei M., Liegibel U. M., Sittlingon J., Rowland I., Wähälä K., Rechkemmer G. Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells. Carcinogenesis 2000; 21, 1247-1252. Go to original source...
    59. American Cancer Society © 2016 citované 2017-11-27). Dostupné na: https://www.cancer.org/cancer/prostate-cancer.html
    60. Normanno N., De Luca A., Bianco C., Strizzi L., Mancino M., Maiello M. R., Carotenuto A., De Feo G., Caponigro F., Salomon D. S. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006; 366, 2-16. Go to original source... Go to PubMed...
    61. Raffoul J. J., Wang Y., Kucuk O., Forman J. D., Sarkar F. H., Hillman G. G. Genistein inhibits radiation-induced activation of NF-κB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest. BMC Cancer 2006; 6, 107. Go to original source... Go to PubMed...
    62. Suzuki K., Koike H., Matsui H., Ono Y., Hasumi M., Nakazato H., Okugi H., Sekine Y., Oki K., Ito K., Yamamoto T., Fukabori Y., Kurokawa K., Yamanaka H. Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP a PC-3. Int. J. Cancer 2002; 99, 846-852. Go to original source... Go to PubMed...
    63. Kumi-Diaka J. Chemosensitivity of human prostate cancer cells PC3 and LNCaP to genistein isoflavone and β-lapachone. Biol. Cell. 2002; 94, 37-44. Go to original source... Go to PubMed...
    64. Hörmann V., Kumi-Diaka J., Durity M., Rathinavelu A. Anticancer activities of genistein-topotecan combination in prostate cancer cells. J. Cell. Mol. Med. 2012; 16, 2631-2636. Go to original source... Go to PubMed...
    65. Gu Y., Zhu C. F., Dai Y. L., Zhong Q., Sun B. Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma. World J. Gastroenterol. 2009; 15, 4952-4957. Go to original source... Go to PubMed...
    66. Gu Y., Zhu C. F., Iwamoto H., Chen J. S. Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis. World J. Gastroenterol. 2005; 11, 6512-6517. Go to original source... Go to PubMed...
    67. Mansoor T. A., Ramalho R. M., Luo X., Ramalhete C., Rodrigues C. M., Ferreira M. J. Isoflavones as apoptosis inducers in human hepatoma HuH-7 cells. Phytother. Res. 2011; 25, 1819-1824. Go to original source... Go to PubMed...
    68. Yeh T. C., Chiang P. C., Li T. K., Hsu J. L., Lin C. J., Wang S. W., Peng C. Y., Guh J. H. Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult. Biochem. Pharmacol. 2007; 73, 782-792. Go to original source... Go to PubMed...
    69. Chodon D., Ramamurty N., Sakthisekaran D. Preliminary studies on induction of apoptosis by genistein on HepG2 cell line. Toxicol. In Vitro 2007; 21, 887-891. Go to original source... Go to PubMed...
    70. Wang S. D., Chen B. C., Kao S. T., Liu C. J., Yeh C. C. Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. BMC Complement. Altern. Med. 2014; 14, 26. Go to original source... Go to PubMed...
    71. Dai W., Wang F., He L., Lin C., Wu S., Chen P., Zhang Y., Shen M., Wu D., Wang C., Lu J., Zhou Y., Xu X., Xu L., Guo C. Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial-mesenchymal transition: partial mediation by the transcription factor NFAT1. Mol. Carcinog. 2015; 54, 301-311. Go to original source... Go to PubMed...
    72. Huang W., Wan C., Luo Q., Huang Z., Luo Q. Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer. Int. J. Mol. Sci. 2014; 15, 3432-3443. Go to original source... Go to PubMed...
    73. Yu D., Shin H. S., Lee Y. S., Lee D., Kim S., Lee Y. C. Genistein attenuates cancer stem cell characteristics in gastric cancer through the down-regulation of Gli1. Oncol. Rep. 2014; 31, 673-678. Go to original source... Go to PubMed...
    74. Zhou H. B., Chen J. J., Wang W. X., Cai J. T., Du Q. Apoptosis of human primary gastric carcinoma cells induced by genistein. World J. Gastroenterol. 2004; 10, 1822-1825. Go to original source... Go to PubMed...
    75. Li Y. S., Wu L. P., Li K. H., Liu Y. P., Xiang R., Zhang S. B., Zhu L. Y., Zhang L. Y. Involvement of nuclear factor kappa B (NF-κB) in the down-regulation of cyclooxygenase-2 (COX-2) by genistein in gastric cancer cells. J. Int. Med. Res. 2011; 39, 2141-2150. Go to original source... Go to PubMed...
    76. Tatsuta M., Iishi H., Baba M., Yano H., Uehara H., Nakaizumi A. Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Int. J. Cancer 1999; 80, 396-399. Go to original source...
    77. American Cancer Society © 2016 citované 2017-11-25). Dostupné na: https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html
    78. Büchler P., Reber H. A., Büchler M. W., Friess H., Lavey R. S., Hines O. J. Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by the inhibition of hypoxia-inducible factor-1 and the down-regulation of VEGF gene expression. Cancer 2004; 100, 201-210. Go to original source... Go to PubMed...
    79. Suzuki R., Kang Y., Li X., Roife D., Zhang R., Fleming J. B. Genistein potentiates the antitumor effect of 5-fluorouracil by inducing apoptosis and autophagy in human pancreatic cancer cells. Anticancer Res. 2014; 34, 4685-4692.
    80. El-Rayes B. F, Ali S., Ali I.F., Philip P. A, Abbruzzese J., Sarkar F. H. Potentiation of the effect of erlotinib by genistein in pancreatic cancer: the role of akt and nuclear factor-KB. Cancer Res. 2006; 66, 10553-10559. Go to original source... Go to PubMed...
    81. Li Y., Ellis K. L., Ali S., El-Rayes B. F., Nedeljkovic-Kurepa A., Kucuk O., Philip P. A., Sarkar F. H. Apoptosis-inducing effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a natural inhibitor of NF-kB in BxPC-3 pancreatic cancer cell line. Pancreas 2004; 28, 90-95. Go to original source... Go to PubMed...
    82. Ma J., Zeng F., Ma C., Pang H., Fang B., Lian C., Yin B., Zhang X., Wang Z., Xia J. Synergistic reversal effect of epithelial-to-mesenchymal transition by miR-223 inhibitor and genistein in gemcitabine-resistant pancreatic cancer cells. Am. J. Cancer Res. 2016; 6, 1384-1395. Go to original source... Go to PubMed...
    83. Tian T., Li J., Li B., Wang Y., Li M., Ma D., Wang X. Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small- cell lung cancer cells. Tumour Biol. 2014; 35, 4137-4145. Go to original source... Go to PubMed...
    84. Yang Y., Zang A., Jia Y., Shang Y., Zhang Z., Ge K., Zhang J., Fan W., Wang B. Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling. Oncol. Lett. 2016; 12: 2189-2193. Go to original source... Go to PubMed...
    85. Shiau, R. J., Chen K. Y., Wen Y. D., Chuang C. H., Yeh S. L. Genistein and β-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells. Eur. J. Nutr. 2010; 49, 19-25. Go to original source... Go to PubMed...
    86. Cheng J., Qi J., Li X. T., Zhou K., Xu J. H., Zhou Y., Zhang G. Q., Xu J. P., Zhou R. J. ATRA and Genistein synergistically inhibit the metastatic potential of human lung adenocarcinoma cells. Int. J. Clin. Exp. Med. 2015; 8, 4220-4227.
    87. Zhu H., Cheng H., Ren Y., Liu Z. G., Zhang Y. F., De Luo B. Synergistic inhibitory effects by the combination of gefitinib and genistein on NSCLC with acquired drug-resistance in vitro and in vivo. Mol. Biol. Rep. 2012; 39, 4971-4979. Go to original source... Go to PubMed...
    88. Stupp R., Mason W. P., van den Bent M. J., Weller M., Fisher B., Taphoorn M. J., Belanger K., Brandes A. A., Marosi C., Bogdahn U., Curschmann J., Janzer R. C., Ludwin S. K., Gorlia T., Allgeier A., Lacombe D., Cairncross J. G., Eisenhauer E., Mirimanoff R. O., European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005; 352, 987-996. Go to original source... Go to PubMed...
    89. Khaw A. K., Yong J. W., Kalthur G., Hande M. P. Genistein Induces Growth Arrest and Suppresses Telomerase Activity in Brain Tumor Cells. Genes Chromosomes Cancer 2012; 51, 961-974. Go to original source... Go to PubMed...
    90. Belcher S. M., Burton C. C., Cookman C. J., Kirby M., Miranda G. L., Saeed F. O., Wray K. E. Estrogen and soy isoflavonoids decrease sensitivity of medulloblastoma and central nervous system primitive neuroectodermal tumor cells to chemotherapeutic cytotoxicity. BMC Pharmacol. Toxicol. 2017; 18, 63. Go to original source... Go to PubMed...
    91. Klauser E., Gülden M., Maser E., Seibert S., Seibert H. Additivity, antagonism, and synergy in arsenic trioxide- induced growth inhibition of C6 glioma cells: Effects of genistein, quercetin and buthionine-sulfoximine. Food Chem. Toxicol. 2014; 67, 212-221. Go to original source... Go to PubMed...
    92. Jeng Y. J., Watson C. S. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases. BMC Cancer 2009; 9, 334. Go to original source... Go to PubMed...
    93. Dvorak H. F. Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 1986; 315, 1650-1659. Go to original source... Go to PubMed...
    94. Dvořánková B., Szabo P., Lacina L., Gál P., Uhrová J., Zima T., Kaltner H., André S., Gabius H. J., Syková E., Smetana Jr. K. Human galectins induce conversion of dermal fibroblasts into myofibroblasts and production of extracellular matrix: Potential application in tissue engineering and wound repair. Cells Tissues Organs 2011; 194, 469-480. Go to original source... Go to PubMed...
    95. Kolář M., Szabo P., Dvořánková B., Lacina L., Gabius H. J., Strnad H., Sáchová J., Vlček C., Plzák J., Chovanec M., Cada Z., Betka J., Fík Z., Pačes J., Kovářová H., Motlík J., Jarkovská K., Smetana Jr. K. Up-regulation of il-6, il-8 and cxcl-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses. Biol. Cell 2012; 104, 738-751. Go to original source... Go to PubMed...
    96. Lacina L., Plzák J., Kodet O., Szabo P., Chovanec M., Dvořánková B., Smetana Jr. K. Cancer microenvironment: What can we learn from the stem cell niche. Int. J. Mol. Sci. 2015; 16, 24094-24110. Go to original source... Go to PubMed...
    97. Emmerson E., Campbell L., Ashcroft G. S., Hardman M. J. The phytoestrogen genistein promotes wound healing by multiple independent mechanisms. Mol. Cell Endocrinol. 2010; 321, 184-193. Go to original source... Go to PubMed...
    98. Ashcroft G. S., Dodsworth J., van Boxtel E., Tarnuzzer R. W., Horan M. A., Schultz G. S., Ferguson M. W. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-beta1 levels. Nat. Med. 1997; 3, 1209-1215. Go to original source... Go to PubMed...
    99. Marini H., Polito F., Altavilla D., Irrera N., Minutoli L., Calò M., Adamo E. B., Vaccaro M., Squadrito F., Bitto A. Genistein aglycone improves skin repair in an incisional model of wound healing: a comparison with raloxifene and oestradiol in ovariectomized rats. Br. J. Pharmacol. 2010; 160, 1185-1194. Go to original source... Go to PubMed...
    100. Renda G., Yalçin F. N., Nemutlu E., Akkol E. K., Süntar I., Keleş H., Ina H., Çaliş I., Ersöz T. Comparative assessment of dermal wound healing potentials of various Trifolium L. extracts and determination of their isoflavone contents as potential active ingredients. J. Ethnopharmacol. 2013; 148, 423-432. Go to original source... Go to PubMed...
    101. Jurzak M., Adamczyk K., Antończak P., Garncarczyk A., Kuśmierz D., Latocha M. Evaluation of genistein ability to modulate CTGF mRNA/protein expression, genes expression of TGFβ isoforms and expression of selected genes regulating cell cycle in keloid fibroblasts in vitro. Acta Pol. Pharm. 2014; 71, 972-986.
    102. Cao C., Li S., Dai X., Chen Y., Feng Z., Zhao Y., Wu J. Genistein inhibits proliferation and functions of hypertrophic scar fibroblasts. Burns 2009; 35, 89-97. Go to original source... Go to PubMed...
    103. Park E., Lee S. M., Jung I. K., Lim Y., Kim J. H. Effects of genistein on early-stage cutaneous wound healing. Biochem. Biophys. Res. Commun. 2011; 410, 514-519. Go to original source... Go to PubMed...
    104. Eo H., Lee H. J., Lim Y. Ameliorative effect of dietary genistein on diabetes induced hyper- inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice. Biochem. Biophys. Res. Commun. 2016; 478, 1021-1027. Go to original source... Go to PubMed...
    105. van der Veldt A. A., Lammertsma A. A., Smit E. F. Scheduling of anticancer drugs: Timing may be everything. Cell Cycle 2012; 11, 4339-4343. Go to original source... Go to PubMed...
    106. Park J. W., Hwang S. R., Yoon I. S. Advanced growth factor delivery systems in wound management and skin regeneration. Molecules 2017; 22, 1259. Go to original source... Go to PubMed...

    Return to the content


    Czech and Slovak Pharmacy

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.