Browse > Article
http://dx.doi.org/10.4014/jmb.0903.0114

2'-Hydroxylation of Genistein Enhanced Antioxidant and Antiproliferative Activities in MCF-7 Human Breast Cancer Cells  

Choi, Jung-Nam (Department of Bioscience and Biotechnology and Bio/Molecular Informatics Center, Konkuk University)
Kim, Doc-Kyu (Polar BioCenter, Korea Polar Research Institute, KORDI)
Choi, Hyung-Kyoon (College of Pharmacy, Chung-Ang University)
Yoo, Kyung-Mi (Department of Bioscience and Biotechnology and Bio/Molecular Informatics Center, Konkuk University)
Kim, Ji-Young (Department of Bioscience and Biotechnology and Bio/Molecular Informatics Center, Konkuk University)
Lee, Choong-Hwan (Department of Bioscience and Biotechnology and Bio/Molecular Informatics Center, Konkuk University)
Publication Information
Journal of Microbiology and Biotechnology / v.19, no.11, 2009 , pp. 1348-1354 More about this Journal
Abstract
Bioconversion of the isoflavonoid genistein to 2'-hydroxygenistein (2'-HG) was performed using isoflavone 2'-hydroxylase (CYP81E1) heterologously expressed in yeast. A monohydroxylated product was analyzed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) and NMR spectrometry and was identified as 2'-HG. An initial bioconversion rate of 6% was increased up to 14% under optimized conditions. After recovery, the biological activity of 2'-HG was evaluated. Bioconverted 2'-HG showed higher antioxidant activity against 1,1-diphenyl-2-picryl hydrazine (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radicals than did genistein. Furthermore, 2'-HG exhibited greater antiproliferative effects in MCF-7 human breast cancer cells than did genistein. These results suggest that 2'-hydroxylation of genistein enhanced its antioxidant activity and cell cytotoxicity in MCF-7 human breast cancer cells.
Keywords
Genistein; 2'-hydroxygenistein; bioconversion; antioxidant activity; antiproliferation activity; MCF-7 cells;
Citations & Related Records

Times Cited By Web Of Science : 0  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Akiyama, T., J. Ishida, S. Nakagawa, H. Ogawara, S. Watanabe, N. Itoh, M. Shibuya, and Y. Fukami. 1987. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Biol. Chem. 262: 5592-5595   PUBMED
2 Cherdshewasart, W. and W. Sutjit, 2008. Correlation of antioxidant activity and major isoflavonoid contents of the phytoestrogen-rich Pueraria mirifica and Pueraria lobata tubers. Phytomedicine 15: 38-43   DOI   ScienceOn
3 Guo, L., R. A. Dixon, and N. L. Paiva. 1994. Conversion of vestitone to medicarpin in alfalfa (Medicago sativa L.) is catalyzed by two independent enzymes. Identification, purification, and characterization of vestitone reductase and 7,2'-dihydroxy4'-methoxyisoflavanol dehydratase. J. Biol. Chem. 269: 22372-22378   PUBMED   ScienceOn
4 Hirota, A., S. Taki, S. Kawaii, M. Yano, and N. Abe. 2000. 1,1-Diphenyl-2-picrylhydrazyl radical-scavenging compounds from soybean miso and antiproliferative activity of isoflavones from soybean miso toward the cancer cell lines. Biosci. Biotechnol. Biochem. 64: 1038-1040   DOI   ScienceOn
5 Kim, H., T. G. Peterson, and S. Barnes. 1998. Mechanisms of action of the soy isoflavone genistein: Emerging role for its effects via transforming growth factor beta signaling pathways. Am. J. Clin. Nutr. 68: 1418S-1425S   PUBMED   ScienceOn
6 Lee, S. K., Z. H. Mbwambo, H. Chung, L. Luyengi, E. J. Gamez, R. G. Mehta, A. D. Kinghorn, and J. M. Pezzuto. 1998. Evaluation of the antioxidant potential of natural products. Comb. Chem. High Throughput Screen. 1: 35-46   PUBMED
7 Li, Y., S. Upadhyay, M. Bhuiyan, and F. H. Sarkar. 1999. Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein. Oncogene 18: 3166-3172   DOI   ScienceOn
8 Peterson, G. and S. Bames. 1996. Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ. 7: 1345-1351   PUBMED
9 Shim, H. Y., J. H. Park, H. D. Paik, S. Y. Nah, D. S. Kim, and Y. S. Han. 2007. Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain-caspase and apoptosis signaling kinase I-p38 mitogen-activated protein kinase activation cascades. Anticancer Drugs 18: 649-657   DOI   ScienceOn
10 Urban, P., C. Mignotte, M. Kazmaier, F. Delorme, and D. Pompon. 1997. Cloning, yeast expression, and characterization of the coupling of two distantly related Arabidopsis thaliana NADPH-cytochrome P450 reductases with P450 CYP73A5. J. Biol. Chem. 272: 19176-19186   DOI   ScienceOn
11 Pompon, D., B. Louerat, A. Bronine, and P. Urban. 1996. Yeast expression of animal and plant P450s in optimized redox environments. Methods Enzymol. 272: 51-64   DOI   PUBMED   ScienceOn
12 Kulling, S. E., D. M. Honig, T. J. Simat, and M. Metzler. 2000. Oxidative in vitro metabolism of the soy phytoestrogens daidzein and genistein. J. Agric. Food Chem. 48: 4963-4972   DOI   ScienceOn
13 Yamamoto, S., K. Shimizu, I. Oonishi, K. Hasebe, H. Takamura, T. Inoue, et al. 1996. Genistein suppresses cellular injury following hepatic ischemialreperfusion. Transplant Proc. 28: 1111-1115   PUBMED   ScienceOn
14 Kulling, S. E., D. M. Honig, and M. Metzler. 2001. Oxidative metabolism of the soy isoflavones daidzein and genistein in humans in vitro and in vivo. J. Agric. Food Chem. 49: 3024-3033   DOI   ScienceOn
15 Shao, Z. M., J. Wu, Z. Z. Shell, and S. H. Barsky. 1998. Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Res. 58: 4851-4857   PUBMED   ScienceOn
16 Ungar, Y., O. F. Osundahunsi, and E. Shimoni. 2003. Thermal stability of genistein and daidzein and its effect on their antioxidant activity. J. Agric. Food Chem. 51: 4394-4399   DOI   ScienceOn
17 Wu, Q., M. Wang, W. J. Sciarappa, and J. E. Simon. 2004. LC/UV/ESI-MS analysis of isoflavones in edamame and tofu soybeans. J. Agric. Food Chem. 52: 2763-2769   DOI   ScienceOn
18 Guo, L., R. A. Dixon, and N. L. Paiva. 1994. The 'pterocarpan synthase' of alfalfa: Association and co-induction of vestitone reductase and 7,2'-dihydroxy-4'-methoxy-isoflavanol (DMI) dehydratase, the two final enzymes in medicarpin biosynthesis. FEBS Lett. 356: 221-225   DOI   PUBMED   ScienceOn
19 Kim, N. Y., E. J. Song, D. Y. Kwon, H. P. Kim, and M. Y. Heo. 2008. Antioxidant and antigenotoxic activities of Korean fermented soybean. Food Chem. Toxicol. 46: 1184-1189   DOI   ScienceOn
20 Strube, M., G. R. Haenen, H. Van Den Berg, and A. Bast. 1997. Pitfalls in a method for assessment of total antioxidant capacity. Free Radic. Res. 26: 515-521   DOI   ScienceOn
21 Engelberg, R. C. D. 2007. Commonly used Saccharomyces cerevisiae strains (e.g., BY4741, W303) are growth sensitive on synthetic complete medium due to poor leucine uptake. FEMS Microbiol. Lett. 273: 239-243   DOI   ScienceOn
22 Rice-Evans, C. A., N. J. Miller, P. G. Bolwell, P. M. Bramley, and J. B. Pridham. 1995. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic. Res. 22: 375-383   DOI   ScienceOn
23 Burda, S. and W. Oleszek. 2001. Antioxidant and antiradical activities of flavonoids. J. Agric. Food Chem. 49: 2774-2779   DOI   ScienceOn
24 Kao, T. H. and B. H. Chen. 2006. Functional components in soybean cake and their effects on antioxidant activity. J. Agric. Food Chem. 54: 7544-7555   DOI   ScienceOn
25 Ralston, L., S. Subramanian, M. Matsuno, and O. Yu. 2005. Partial reconstruction of flavonoid and isoflavonoid biosynthesis in yeast using soybean type I and type II chalcone isomerases. Plant Physiol. 137: 1375-1388   DOI   ScienceOn
26 Sarkar, F. H. and Y. Li. 2003. Soy isoflavones and cancer prevention. Cancer Invest. 21: 744-757   DOI   ScienceOn
27 Arora, A., M. G. Nair, and G. M. Strasburg. 1998. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch. Biochem. Biophys. 356: 133-141   DOI   ScienceOn
28 Ruiz-Larrea, M. B., A. R. Mohan, G Paganga, N. J. Miller, G. P. Bolwell, and C. A. Rice-Evans. 1997. Antioxidant activity of phytoestrogenic isoflavones. Free Radic. Res. 26: 63-70   DOI   ScienceOn
29 Harbome, J. B. and C. A. Williams. 2000. Advances in flavonoid research since 1992. Phytochemistry 55: 481-504   DOI   ScienceOn
30 Cassidy, A., S. Bingham, and K. Setchell. 1995. Biological effects of isoflavones in young women: Importance of the chemical composition of soyabean products. Br. J. Nutr. 74: 587-601   DOI   ScienceOn
31 Sarkar, F. H. and Y. Li. 2002. Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev. 21: 265-280   DOI   ScienceOn
32 Wei, H., R. Bowen, Q. Cai, S. Bames, and Y. Wang. 1995. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc. Soc. Exp. Biol. Med. 208: 124-130   PUBMED   ScienceOn
33 Akashi, T., T. Aoki, and S. Ayabe. 1998. CYP81El, a cytochrome P450 cDNA of licorice (Glycyrrhiza echinata L.), encodes isoflavone 2'-hydroxylase. Biochem. Biophys. Res. Commun. 251: 67-70   DOI   ScienceOn
34 Jiang, H. and J. A. Morgan. 2004. Optimization of an in vivo plant P450 monooxygenase system in Saccharomyces cerevisiae. Biotechnol. Bioeng. 85: 130-137   DOI   ScienceOn
35 Fritz, W. A., L. Coward, J. Wang, and C. A. Lamartiniere. 1998. Dietary genistein: Perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis 19: 2151-2158   DOI   ScienceOn
36 Lee, J. S., D. H. Kim, K. H. Liu, T. K. Oh, and C. H. Lee. 2005. Identification of flavonoids using liquid chromatography with electrospray ionization and ion trap tandem mass spectrometry with an MSIMS library. Rapid Commun. Mass Spectrom. 19: 3539-3548   DOI   ScienceOn
37 Yamashita, Y., S. Kawada, and H. Nakano. 1990. Induction of mammalian topoisomerase II dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol. Biochem. Pharmacol. 39: 737-744   DOI   ScienceOn