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Antioxidant and anticancer activity of 3,5-dihydroxy-4-isopropylstilbene produced by Bacillus sp. N strain isolated from entomopathogenic nematode

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Abstract

3,5-Dihydroxy-4-isopropylstilbene is a natural phytoalexin and was first identified as bacterial secondary metabolites. The aim of this study is to investigate in vitro antioxidant and anticancer activity of 3,5-dihydroxy-4-isopropystilbene purified from the cell free culture filtrate of Bacillus sp. N strain associated with rhabditid entomopathogenic nematode. Antioxidant activity was evaluated by five separate methods: free radical scavenging, reducing power assay, chelating effects on ferrous ions, NBT superoxide radical scavenging assay and hydroxyl radical scavenging activity. The stilbene recorded powerful antioxidant activity at various antioxidant systems in vitro. The superoxide radical scavenging (92.1 %) and hydroxyl radical scavenging (83.4 %) activities of the stilbenes at 100 μg/ml were higher than the butylated hydroxyanisole, the known antioxidant agent. Anticancer activity of stilbene was tested against breast cancer (MDAM B-231), cervical cancer (HeLa), lung cancer (A 549), colon cancer (HTL 116) cell lines using MTT method. The induction of apoptosis was studied by morphological analysis, apoptotic cell staining, caspase 3 activation assay and cell cycle analysis using flow cytometry. Stilbene induced significant morphological changes and DNA fragmentation associated with apoptosis in HeLa cells. Acridine orange/ethidium bromide stained cells indicated apoptosis induction by stilbene. Up-regulation of caspase 3 activity was also found in cells treated with stilbene. Flow cytometry analysis showed an increase in the percentage of apoptotic cells in sub G0 phase (2.4 % in control plates to 11.4 % in 25 μg/ml of stilbene) confirming the stilbene induced apoptosis. The results of the present study showed that stilbene demonstrated a strong antioxidant and anticancer effects. These suggest that stilbene may be used as possible natural antioxidant and anticancer agents to control various human diseases.

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References

  • Ahmad, A., F.A. Syed, S. Singh, and S.M. Hadi. 2005. Prooxidant activity of resveratrol in the presence of copper ions: Mutagenicity in plasmid DNA. Toxicology Letters 159: 1–12.

    Article  PubMed  CAS  Google Scholar 

  • Alarco′n de la Lastra, C., and I. Villegas. 2007. Resveratrol as an antioxidant and pro-oxidant agent: Mechanisms and clinical implications. Biochemical Society Transactions 35: 1156–1160.

    Article  PubMed  Google Scholar 

  • Anto, R.J., M. Venkataraman, and D. Karunagaran. 2003. Inhibition of NF-KB Sensitizes A431 cells to epidermal growth factor-induced apoptosis, whereas its activation by ectopic expression of RelA confers resistance. Journal of Biological Chemistry 28: 25490–25498.

    Article  CAS  Google Scholar 

  • Butler, M.S. 2005. Natural products to drugs: Natural product derived compounds in clinical trials. Natural Products Reports 22: 162–195.

    Article  CAS  Google Scholar 

  • Butler, M.S. 2008. Natural products to drugs: Natural product-derived compounds in clinical trials. Natural Products Reports 25: 475–516.

    Article  CAS  Google Scholar 

  • Carlsen, M.H., B.L. Halvorsen, K. Holteet, S.K. Bøhn, S. Dragland, L. Sampson, C. Willey, H. Senoo, Y. Umezono, C. Sanada, I. Barikmo, N. Berhe, W.C. Willett, K.M. Phillips, D.R. Jacobs, and R. Blomhof. 2010. The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutrition Journal 9: 1–11.

    Article  CAS  Google Scholar 

  • Chung, S.K., T. Osawa, and S. Kawakishi. 1997. Hydroxyl radical scavenging effects of species and scavengers from brown mustard (Brassica nigra). Bioscience Biotechnology and Biochemistry 61: 118–123.

    Article  CAS  Google Scholar 

  • Cohen, J.J. 1991. Programmed cell death in the immune system. Advances in Immunology 50: 55–85.

    Article  PubMed  CAS  Google Scholar 

  • Cragg, G.M., D.G.I. Kingston, and D.J. Newman. 2005. Anticancer agents from natural products. Boca Raton: CRC Press.

    Book  Google Scholar 

  • Dinis, T.C.P., V.M.C. Madeira, and L.M. Almeida. 1994. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Archives of Biochemistry and Biophysics 315: 161–169.

    Article  PubMed  CAS  Google Scholar 

  • Finkel, T., and N.J. Holbrook. 2000. Oxidants, oxidative stress and the biology of aging. Nature 408(6809): 239–247.

    Article  PubMed  CAS  Google Scholar 

  • Girotti, A.W. 1998. Lipid hydroperoxide generation, turnover, and effector action in biological systems. Journal of Lipid Research 39: 1529–1542.

    Article  PubMed  CAS  Google Scholar 

  • Grice, H.C. 1986. Safety evaluation of butylated hydroxytoluene (BHT) in the liver, lung and gastrointestinal tract. Food and Chemical Toxicology 24: 1127–1130.

    Article  Google Scholar 

  • Gülcin, O., M. Kufrevio, S. Oktay, and M.E. Buyukokuro. 2004. Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.). Journal of Ethnopharmacology 90: 205–215.

    Article  PubMed  Google Scholar 

  • Hagiwara, K., K. Nobuyoshi, Y. Yoshioka, R. Takahashi, F. Takeshita, and T. Ochiya. 2012. Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity. Scientific Reports 314: 1–8.

    Google Scholar 

  • Halliwell, B., R. Aeschbach, J. Loligeret, and O.I. Aruoma. 1995. The characterization of antioxidants. Food and Chemical Toxicology 33: 601–617.

    Article  PubMed  CAS  Google Scholar 

  • Hu, K., and J.M. Webster. 2000. Antibiotic production in relation to bacterial growth and nematode development in Photorhabdus-Heterorhabditis infected Galleria mellonella larvae. FEMS Microbiology Letters 189: 219–223.

    PubMed  CAS  Google Scholar 

  • Hu, K.J., J.X. Li, and W.J. Wand. 1998. Comparison of metabolites produced in vitro and in vivo by Photorhabdus luminescens, a bacterial symbiont of the entomopathogenic nematode Heterorhabditis megidis. Canadian Journal of Microbiology 44: 1072–1077.

    Article  CAS  Google Scholar 

  • Kannan, R.R.R., R. Arumugam, and P. Anantharaman. 2010. In vitro antioxidant activities of ethanol extract from Enhalus acoroides (L.F.) Royle. Asian Pacific Journal of Tropical Medicine 3(11): 898–901.

    Article  Google Scholar 

  • Kerr, J.F., A.H. Wyllie, and A.R. Currie. 1972. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26(4): 239–257.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kinsella, J.E., E. Frankel, B. German, and J. Kanner. 1993. Possible mechanism for the protective role of the antioxidant in wine and plant foods. Food Technology 47: 85–89.

    CAS  Google Scholar 

  • Kohen, R., and A. Nyska. 2002. Oxidation of biological systems: Oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicologic Pathology 30: 620–650.

    Article  PubMed  CAS  Google Scholar 

  • Konzen, M., D. De Marco, C.A.S. Cordova, T.O. Vieira, R.V. Antonio, and T.B. Creczynski-Pasa. 2006. Antioxidant properties of violacein: Possible relation on its biological function. Bioorganic and Medicinal Chemistry 14: 8307–8313.

    Article  PubMed  CAS  Google Scholar 

  • Kuate, D., B.C.O. Etoundi, Y.B. Soukontoua, J.L. Ngondi, and J.E. Oben. 2010. Antioxidant characteristics of Dichrostachys glomerata spice extracts. CyTA—Journal of Food 8: 23–37.

    Article  CAS  Google Scholar 

  • Kumar, R., D.D. Bansal, D.D. Patel, S. Mishra, Y. Karamalakova, A. Zheleva, V. Gadjeva, and R.K. Sharma. 2011. Antioxidative and radioprotective activities of semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1. Molecular and Cellular Biochemistry 349(1–2): 57–67.

    Article  PubMed  CAS  Google Scholar 

  • Kumar, S.N., J.V. Siji, B. Nambisan, K.N. Rajasekharan, and C. Mohandas. 2012. Bioactive stilbenes from a Bacillus sp. N strain associated with a novel rhabditid entomopathogenic nematode. Letters Applied Microbiology 54: 410–417.

    Article  CAS  Google Scholar 

  • Lai, L.S., S.T. Chou, and W.W. Chao. 2001. Studies on the antioxidative activities of Hsian-tsao (Mesona procumbens Hemsl) leaf gum. Journal of Agriculture and Food Chemistry 49: 963–968.

    Article  CAS  Google Scholar 

  • Lee, J.Y., W.I. Hwang, and S.T. Lim. 2004. Antioxidant and anticancer activities of extracts from Platycodon grandiflorum A. de Candolle roots. Journal of Ethnopharmacology 93: 409–415.

    Article  PubMed  Google Scholar 

  • Li, J., G.H. Chen, H.M. Wu, and J.M. Webster. 1995. Identification of two pigments and a hydroxystilbene antibiotic from Photorhabdus luminescens. Applied and Environment Microbiology 61: 4329–4333.

    Article  CAS  Google Scholar 

  • Liu, F., and T.B. Ng. 2000. Antioxidative and free radical scavenging activities of selected medicinal herbs. Life Sciences 66: 725–735.

    Article  PubMed  CAS  Google Scholar 

  • Liu, F., V.E.C. Ooi, and S.T. Chang. 1997. Free radical scavenging activities of mushroom polysaccharide extracts. Life Sciences 60: 763–771.

    Article  PubMed  CAS  Google Scholar 

  • Liu, J., C. Wang, Z. Wang, C. Zhang, S. Lu, and J. Liu. 2011. The antioxidant and free-radical scavenging activities of extract and fractions from corn silk (Zea mays L.) and related flavone glycosides. Food Chemistry 126: 261–269.

    Article  CAS  Google Scholar 

  • Lockshin, R.A., and Z. Zakeri. 2002. Caspase-independent cell deaths. Current Opinion in Cell Biology 14(6): 727–733.

    Article  PubMed  CAS  Google Scholar 

  • Nawar, W.F. 1996. Lipids. In Food chemistry, 3rd ed, ed. O. Fennema, 225–320. New York: Marcel Dekker Inc.

    Google Scholar 

  • Newman, D.J., and G.M. Cragg. 2007. Natural product as source of new drugs over the last 25 years. Journal of Natural Products 70: 461–477.

    Article  PubMed  CAS  Google Scholar 

  • Oktay, M., J. Gulcin, and O. Kufrevio. 2003. Determination of in vitro antioxidant activity of fennel (Foeniculum vulgare) seed extracts. LWT. Food Science and Technology 36: 263–271.

    Article  CAS  Google Scholar 

  • Oyaizu, M. 1986. Studies on product of browning reaction prepared from glucose amine. Japanese Journal of Nutrition 44: 307–315.

    Article  CAS  Google Scholar 

  • Richardson, W.H., T.M. Schmidt, and K.H. Nealson. 1988. Identification of an anthraquinone pigment and a hydroxystilbene antibiotic from Xenorhabdus luminescens. Applied and Environment Microbiology 54: 1602–1605.

    Article  CAS  Google Scholar 

  • Sherwin, E.R., A.L. Branen, P.M. Davidson, and S. Salminen. 1990. Food additives, 139–193. New York: Marvel Dekker Inc.

    Google Scholar 

  • Tadhani, M.B., V.H. Patel, and R. Subhash. 2007. In vitro antioxidant activities of Stevia rebaudiana leaves and callus. Journal of Food Composition and Analysis 20: 323–329.

    Article  CAS  Google Scholar 

  • Tang, L.R., G.H. Chen, J. Li, and B. Webster. 2007. Anti-inflammatory activities of stilbene analogs for targeting autoimmune diseases. Clinical Immunology 123: S124.

    Article  Google Scholar 

  • Watanabe, M., and T.S. Todo. 2008. The novel antioxidant edaravone: From bench 435 to bedside. Cardiovascular Therapeutics 26: 101–114.

    Article  PubMed  CAS  Google Scholar 

  • Wyllie, A.H. 1980. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555–556.

    Article  PubMed  CAS  Google Scholar 

  • Yen, G.C., and H.Y. Chen. 1995. Antioxidant activity of various tea extracts in relation to their antimutagenicity. Journal of Agriculture and Food Chemistry 43: 27–32.

    Article  CAS  Google Scholar 

  • Yoshida, H., H. Yanai, Y. Namiki, K. Fukatsu-Sasaki, N. Furutani, and N. Tada. 2006. Neuroprotective effects of edaravone: A novel free radical scavenger in cerebrovascular injury. CNS Drug Reviews 438: 9–20.

    Article  Google Scholar 

  • Zhang, E.X., L.J. Yu, Y.L. Zhou, and X. Xiao. 1996. Studies on the peroxidation of polyunsaturated fatty acid from lipoprotein induced by iron and the evaluation of 444 the anti-oxidative activity of some natural products. Acta Biochimica et Biophysica Sinica 28: 218–222.

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to Indian Council Medical Research (ICMR), Government of India for funding. We thank the Director, CTCRI, for providing facilities for the work.

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Authors declared no conflict of interest.

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Authors and Affiliations

  1. Division of Crop Protection/Division of Crop Utilisation, Central Tuber Crops Research Institute, Sreekariyam, Thiruvananthapuram, 695017, India

    Sasidharan Nishanth Kumar, Bala Nambisan & Chellapan Mohandas

  2. Division of Agroprocessing and Natural Products, National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India

    B. S. Dileep Kumar & Nisha Girija Vasudevan

  3. Integrated Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India

    Vino T. Cheriyan & Ruby John Anto

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  1. Sasidharan Nishanth Kumar
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Kumar, S.N., Nambisan, B., Kumar, B.S.D. et al. Antioxidant and anticancer activity of 3,5-dihydroxy-4-isopropylstilbene produced by Bacillus sp. N strain isolated from entomopathogenic nematode. Arch. Pharm. Res. (2013). https://doi.org/10.1007/s12272-013-0207-2

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