Biomolecules & Therapeutics

  • 제27권6호
  • /
  • Pages.540-552
  • /
  • 2019
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Alyssin and Iberin in Cruciferous Vegetables Exert Anticancer Activity in HepG2 by Increasing Intracellular Reactive Oxygen Species and Tubulin Depolymerization

  • Pocasap, Piman (Research and Development in Pharmaceuticals Program, Graduate School, Faculty of Pharmaceutical Sciences, Khon Kaen University) ;
  • Weerapreeyakul, Natthida (Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University) ;
  • Thumanu, Kanjana (Synchrotron Light Research Institute (Public Organization))
  • 투고 : 2019.02.12
  • 심사 : 2019.06.17
  • 발행 : 2019.11.01
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초록

To determine the chemopreventive potential of alyssin and iberin, the in vitro anticancer activities and molecular targets of isothiocyanates (ITCs) were measured and compared to sulforaphane in hepatocellular carcinoma cell HepG2. The SR-FTIR spectra observed a similar pattern vis-a-vis the biomolecular alteration amongst the ITCs-treated cells suggesting a similar mode of action. All of the ITCs in this study cause cancer cell death through both apoptosis and necrosis in concentration dependent manner ($20-80{\mu}M$). We found no interactions of any of the ITCs studied with DNA. Notwithstanding, all of the ITCs studied increased intracellular reactive oxygen species (ROS) and suppressed tubulin polymerization, which led to cell-cycle arrest in the S and $G_2/M$ phase. Alyssin possessed the most potent anticancer ability; possibly due to its ability to increase intracellular ROS rather than tubulin depolymerization. Nevertheless, the structural influence of alkyl chain length on anticancer capabilities of ITCs remains inconclusive. The results of this study indicate an optional, potent ITC (viz., alyssin) because of its underlying mechanisms against hepatic cancer. As a consequence, further selection and development of effective chemotherapeutic ITCs is recommended.

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참고문헌

  1. Abassi Joozdani, F., Yari, F., Abassi Joozdani, P. and Nafisi, S. (2015) Interaction of sulforaphane with DNA and RNA. PLoS ONE 10, e0127541. https://doi.org/10.1371/journal.pone.0127541
  2. Agarwal, S., Jangir, D. K. and Mehrotra, R. (2013) Spectroscopic studies of the effects of anticancer drug mitoxantrone interaction with calf-thymus DNA. J. Photochem. Photobiol. B Biol. 120, 177-182. https://doi.org/10.1016/j.jphotobiol.2012.11.001
  3. Al-Qenaei, A., Yiakouvaki, A., Reelfs, O., Santambrogio, P., Levi, S., Hall, N. D., Tyrrell, R. M. and Pourzand, C. (2014) Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide. Free Radic. Biol. Med. 68, 87-100. https://doi.org/10.1016/j.freeradbiomed.2013.12.006
  4. Angelino, D. and Jeffery, E. (2014) Glucosinolate hydrolysis and bioavailability of resulting isothiocyanates: focus on glucoraphanin. J. Funct. Foods 7, 67-76. https://doi.org/10.1016/j.jff.2013.09.029
  5. Azarenko, O., Jordan, M. A. and Wilson, L. (2014) Erucin, the major isothiocyanate in arugula (Eruca sativa), inhibits proliferation of MCF7 tumor cells by suppressing microtubule dynamics. PLoS ONE 9, e100599. https://doi.org/10.1371/journal.pone.0100599
  6. Baker, M. J., Trevisan, J., Bassan, P., Bhargava, R., Butler, H. J., Dorling, K. M., Fielden, P. R., Fogarty, S. W., Fullwood, N. J., Heys, K. A., Hughes, C., Lasch, P., Martin-Hirsch, P. L., Obinaju, B., Sockalingum, G. D., Sule-Suso, J., Strong, R. J., Walsh, M. J., Wood, B. R., Gardner, P. and Martin, F. L. (2014) Using Fourier transform IR spectroscopy to analyze biological materials. Nat. Protoc. 9, 1771-1791. https://doi.org/10.1038/nprot.2014.110
  7. Blazevic, I., Montaut, S., Burcul, F. and Rollin, P. (2016) Glucosinolates: novel sources and biological potential. In Glucosinolates (J. M. Merillon and K. G. Ramawat Eds.), pp. 1-58. Springer International Publishing, Cham.
  8. Clarke, J. D., Hsu, A., Yu, Z., Dashwood, R. H. and Ho, E. (2011) Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol. Nutr. Food Res. 55, 999-1009. https://doi.org/10.1002/mnfr.201000547
  9. Clarke, P. R. and Allan, L. A. (2009) Cell-cycle control in the face of damage - a matter of life or death. Trends Cell Biol. 19, 89-98. https://doi.org/10.1016/j.tcb.2008.12.003
  10. Di Giambattista, L., Pozzi, D., Grimaldi, P., Gaudenzi, S., Morrone, S. and Congiu Castellano, A. (2011) New marker of tumor cell death revealed by ATR-FTIR spectroscopy. Anal. Biol. Chem. 399, 2771-2778. https://doi.org/10.1007/s00216-011-4654-7
  11. Ernst, I. M. A., Palani, K., Esatbeyoglu, T., Schwarz, K. and Rimbach, G. (2013) Synthesis and Nrf2-inducing activity of the isothiocyanates iberverin, iberin and cheirolin. Pharmacol. Res. 70, 155-162. https://doi.org/10.1016/j.phrs.2013.01.011
  12. Ferreira de Oliveira, J. M. P., Costa, M., Pedrosa, T., Pinto, P., Remedios, C., Oliveira, H., Pimentel, F., Almeida, L. and Santos, C. (2014) Sulforaphane induces oxidative stress and death by p53-independent mechanism: implication of impaired glutathione recycling. PLoS ONE 9, e92980. https://doi.org/10.1371/journal.pone.0092980
  13. Galadari, S., Rahman, A., Pallichankandy, S. and Thayyullathil, F. (2017) Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic. Biol. Med. 104, 144-164. https://doi.org/10.1016/j.freeradbiomed.2017.01.004
  14. Gao, Y., Huo, X., Dong, L. I. U., Sun, X., Sai, H. E., Wei, G., Xu, Y., Zhang, Y. and Wu, J. (2015) Fourier transform infrared microspectroscopy monitoring of 5-fluorouracil-induced apoptosis in SW620 colon cancer cells. Mol. Med. Rep. 11, 2585-2591. https://doi.org/10.3892/mmr.2014.3088
  15. Gasper, R., Dewelle, J., Kiss, R., Mijatovic, T. and Goormaghtigh, E. (2009) IR spectroscopy as a new tool for evidencing antitumor drug signatures. Biochim. Biophys. Acta 1788, 1263-1270. https://doi.org/10.1016/j.bbamem.2009.02.016
  16. Gasper, R., Vandenbussche, G. and Goormaghtigh, E. (2011) Ouabain- induced modifications of prostate cancer cell lipidome investigated with mass spectrometry and FTIR spectroscopy. Biochem. Biophys. Acta 1808, 597-605. https://doi.org/10.1016/j.bbamem.2010.11.033
  17. Gross-Steinmeyer, K., Stapleton, P. L., Tracy, J. H., Bammler, T. K., Strom, S. C. and Eaton, D. L. (2010) Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. Toxicol. Sci. 116, 422-432. https://doi.org/10.1093/toxsci/kfq135
  18. Gupta, P., Wright, S. E., Kim, S. H. and Srivastava, S. K. (2014) Phenethyl isothiocyanate: a comprehensive review of anti-cancer mechanisms. Biochem. Biophys. Acta 1846, 405-424.
  19. Hahm, E. R., Chandra-Kuntal, K., Desai, D., Amin, S. and Singh, S. V. (2012) Notch activation is dispensable for D, L-sulforaphanemediated inhibition of human prostate cancer cell migration. PLoS ONE 7, e44957. https://doi.org/10.1371/journal.pone.0044957
  20. Hahm, E. R. and Singh, S. V. (2010) Sulforaphane inhibits constitutive and interleukin-6-induced activation of signal transducer and activator of transcription 3 in prostate cancer cells. Cancer Prev. Res. (Phila.) 3, 484-494. https://doi.org/10.1158/1940-6207.CAPR-09-0250
  21. Hou, D. X., Fukuda, M., Fujii, M. and Fuke, Y. (2000) Induction of NADPH:quinone oxidoreductase in murine hepatoma cells by methylsulfinyl isothiocyanates: methyl chain length-activity study. Int. J. Mol. Med. 6, 441-444.
  22. Jadhav, U., Ezhilarasan, R., Vaughn, S. F., Berhow, M. A. and Mohanam, S. (2007) Iberin induces cell cycle arrest and apoptosis in human neuroblastoma cells. Int. J. Mol. Med. 19, 353-361.
  23. Jakubikova, J., Bao, Y., Bodo, J. and Sedlak, J. (2006) Isothiocyanate iberin modulates phase II enzymes, posttranslational modification of histones and inhibits growth of Caco-2 cells by inducing apoptosis. Neoplasma 53, 463-470.
  24. Jiao, D., Eklind, K. I., Choi, C. I., Desai, D. H., Amin, S. G. and Chung, F. L. (1994) Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Cancer Res. 54, 4327-4333.
  25. Junhom, C., Weerapreeyakul, N., Tanthanuch, W. and Thumanu, K. (2016) FTIR microspectroscopy defines early drug resistant human hepatocellular carcinoma (HepG2) cells. Exp. Cell Res. 340, 71-80. https://doi.org/10.1016/j.yexcr.2015.12.007
  26. Kallifatidis, G., Labsch, S., Rausch, V., Mattern, J., Gladkich, J., Moldenhauer, G., Büchler, M. W., Salnikov, A. V. and Herr, I. (2011) Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol. Ther. 19, 188-195. https://doi.org/10.1038/mt.2010.216
  27. Kaschula, C. H. and Hunter, R. (2016) Chapter 1 - Synthesis and structure-activity relations in allylsulfide and isothiocyanate compounds from garlic and broccoli against in vitro cancer cell growth. In Studies in Natural Products Chemistry (R. Atta-ur Ed.), pp. 1-43. Elsevier.
  28. La Marca, M., Beffy, P., Della Croce, C., Gervasi, P. G., Iori, R., Puccinelli, E. and Longo, V. (2012) Structural influence of isothiocyanates on expression of cytochrome P450, phase II enzymes, and activation of Nrf2 in primary rat hepatocytes. Food Chem. Toxicol. 50, 2822-2830. https://doi.org/10.1016/j.fct.2012.05.044
  29. Lamberti, A., Sanges, C. and Arcari, P. (2010) FT-IR spectromicroscopy of mammalian cell cultures during necrosis and apoptosis induced by drugs. Spectroscopy 24, 535-546. https://doi.org/10.1155/2010/420791
  30. Luang-In, V. and Rossiter, J. T. (2015) Stability studies of isothiocyanates and nitriles in aqueous media. Songklanakarin J. Sci. Technol. 37, 625-630.
  31. Machana, S., Weerapreeyakul, N., Barusrux, S., Thumanu, K. and Tanthanuch, W. (2012) FTIR microspectroscopy discriminates anticancer action on human leukemic cells by extracts of Pinus kesiya; Cratoxylum formosum ssp. pruniflorum and melphalan. Talanta 93, 371-382. https://doi.org/10.1016/j.talanta.2012.02.058
  32. Matsui, T. A., Sowa, Y., Yoshida, T., Murata, H., Horinaka, M., Wakada, M., Nakanishi, R., Sakabe, T., Kubo, T. and Sakai, T. (2006) Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells. Carcinogenesis 27, 1768-1777. https://doi.org/10.1093/carcin/bgl015
  33. Mi, L., Di Pasqua, A. J. and Chung, F. L. (2011) Proteins as binding targets of isothiocyanates in cancer prevention. Carcinogenesis 32, 1405-1413. https://doi.org/10.1093/carcin/bgr111
  34. Mi, L., Gan, N., Cheema, A., Dakshanamurthy, S., Wang, X., Yang, D. C. and Chung, F. L. (2009) Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes. J. Biol. Chem. 284, 17039-17051. https://doi.org/10.1074/jbc.M901789200
  35. Mi, L., Xiao, Z., Hood, B. L., Dakshanamurthy, S., Wang, X., Govind, S., Conrads, T. P., Veenstra, T. D. and Chung, F. L. (2008) Covalent binding to tubulin by isothiocyanates. A mechanism of cell growth arrest and apoptosis. J. Biol. Chem. 283, 22136-22146. https://doi.org/10.1074/jbc.M802330200
  36. Miller, L. M., Bourassa, M. W. and Smith, R. J. (2013) FTIR spectroscopic imaging of protein aggregation in living cells. Biochim. Biophys. Acta 1828, 2339-2346. https://doi.org/10.1016/j.bbamem.2013.01.014
  37. Misiewicz, I., Skupinska, K. and Kasprzycka-Guttman, T. (2007) Differential response of human healthy lymphoblastoid and CCRF-SB leukemia cells to sulforaphane and its two analogues: 2-oxohexyl isothiocyanate and alyssin. Pharmacol. Rep. 59, 80-87.
  38. Mourant, J. R., Yamada, Y. R., Carpenter, S., Dominique, L. R. and Freyer, J. P. (2003) FTIR spectroscopy demonstrates biochemical differences in mammalian cell cultures at different growth stages. Biophys. J. 85, 1938-1947. https://doi.org/10.1016/S0006-3495(03)74621-9
  39. Nonpunya, A., Sethabouppha, B., Rufini, S. and Weerapreeyakul, N. (2018) Cratoxylum formosum ssp. pruniflorum activates the TRAIL death receptor complex and inhibits topoisomerase I. S. Afr. J. Bot. 114, 150-162. https://doi.org/10.1016/j.sajb.2017.11.003
  40. Park, H. S., Han, M. H., Kim, G. Y., Moon, S. K., Kim, W. J., Hwang, H. J., Park, K. Y. and Choi, Y. H. (2014) Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells. Food Chem. Toxicol. 64, 157-165. https://doi.org/10.1016/j.fct.2013.11.034
  41. Pocasap, P., Weerapreeyakul, N. and Barusrux, S. (2013) Cancer preventive effect of Thai rat-tailed radish (Raphanus sativus L. var. caudatus Alef). J. Funct Foods 5, 1372-1381. https://doi.org/10.1016/j.jff.2013.05.005
  42. Pocasap, P., Weerapreeyakul, N. and Thumanu, K. (2018) Structures of isothiocyanates attributed to reactive oxygen species generation and microtubule depolymerization in HepG2 cells. Biomed. Pharmacother. 101, 698-709. https://doi.org/10.1016/j.biopha.2018.02.132
  43. Prakash, D. and Gupta, C. (2012) Glucosinolates: the phytochemicals of nutraceutical importance. J. Complement. Integr. Med. 9, Article 13.
  44. Rajendran, P., Kidane, A. I., Yu, T.-W., Dashwood, W.-M., Bisson, W. H., Löhr, C. V., Ho, E., Williams, D. E. and Dashwood, R. H. (2013) HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates. Epigenetics 8, 612-623. https://doi.org/10.4161/epi.24710
  45. Sestili, P. and Fimognari, C. (2015) Cytotoxic and antitumor activity of sulforaphane: the role of reactive oxygen species. BioMed Res. Int. 2015, 9.
  46. Shang, H. S., Shih, Y. L., Lee, C. H., Hsueh, S. C., Liu, J. Y., Liao, N. C., Chen, Y. L., Huang, Y. P., Lu, H. F. and Chung, J. G. (2017) Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ. Toxicol. 32, 311-328. https://doi.org/10.1002/tox.22237
  47. Shibata, T., Kimura, Y., Mukai, A., Mori, H., Ito, S., Asaka, Y., Oe, S., Tanaka, H., Takahashi, T. and Uchida, K. (2011) Transthiocarbamoylation of proteins by thiolated isothiocyanates. J. Biol. Chem. 286, 42150-42161. https://doi.org/10.1074/jbc.M111.308049
  48. Skupinska, K., Misiewicz-Krzeminska, I., Lubelska, K. and Kasprzycka-Guttman, T. (2009) The effect of isothiocyanates on CYP1A1 and CYP1A2 activities induced by polycyclic aromatic hydrocarbons in Mcf7 cells. Toxicol. In Vitro 23, 763-771. https://doi.org/10.1016/j.tiv.2009.04.001
  49. Tian, G., Li, Y., Cheng, L., Yuan, Q., Tang, P., Kuang, P. and Hu, J. (2016) The mechanism of sulforaphene degradation to different water contents. Food Chem. 194, 1022-1027. https://doi.org/10.1016/j.foodchem.2015.08.107
  50. Traka, M. H. (2016) Health benefits of glucosinolates. Adv. Bot. Res. 80, 247-279. https://doi.org/10.1016/bs.abr.2016.06.004
  51. Veeranki, O. L., Bhattacharya, A., Tang, L., Marshall, J. R. and Zhang, Y. (2015) Cruciferous vegetables, isothiocyanates, and prevention of bladder bancer. Curr. Pharmacol. Rep. 1, 272-282. https://doi.org/10.1007/s40495-015-0024-z
  52. Verbon, E. H., Post, J. A. and Boonstra, J. (2012) The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene 511, 1-6. https://doi.org/10.1016/j.gene.2012.08.038
  53. Wang, W., Wang, S., Howie, A. F., Beckett, G. J., Mithen, R. and Bao, Y. (2005) Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression in human MCF-7 cells. J. Agric. Food Chem. 53, 1417-1421. https://doi.org/10.1021/jf048153j
  54. Wu, X., Zhou, Q. H. and Xu, K. (2009) Are isothiocyanates potential anti-cancer drugs? Acta Pharmacol. Sin. 30, 501-512. https://doi.org/10.1038/aps.2009.50
  55. Xiao, D., Powolny, A. A., Moura, M. B., Kelley, E. E., Bommareddy, A., Kim, S. H., Hahm, E. R., Normolle, D., Van Houten, B. and Singh, S. V. (2010) Phenethyl isothiocyanate inhibits oxidative phosphorylation to trigger reactive oxygen species-mediated death of human prostate cancer cells. J. Biol. Chem. 285, 26558-26569. https://doi.org/10.1074/jbc.M109.063255
  56. Xiao, D., Powolny, A. A. and Singh, S. V. (2008) Benzyl isothiocyanate targets mitochondrial respiratory chain to trigger reactive oxygen species-dependent apoptosis in human breast cancer cells. J. Biol. Chem. 283, 30151-30163. https://doi.org/10.1074/jbc.M802529200
  57. Zelig, U., Kapelushnik, J., Moreh, R., Mordechai, S. and Nathan, I. (2009) Diagnosis of cell death by means of infrared spectroscopy. Biophys. J. 97, 2107-2114. https://doi.org/10.1016/j.bpj.2009.07.026
  58. Zhou, T., Li, G., Cao, B., Liu, L., Cheng, Q., Kong, H., Shan, C., Huang, X., Chen, J. and Gao, N. (2013) Downregulation of Mcl-1 through inhibition of translation contributes to benzyl isothiocyanate-induced cell cycle arrest and apoptosis in human leukemia cells. Cell Death Dis. 4, e515. https://doi.org/10.1038/cddis.2013.41

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