DOI QR코드

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Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana

  • Kim, Mi Seon (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Lee, Yunmi (Department of Chemistry, Kwangwoon University) ;
  • Sung, Gi-Ho (Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University) ;
  • Kim, Ji Hye (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Park, Jae Gwang (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Kim, Han Gyung (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Baek, Kwang Soo (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Cho, Jae Han (Mushroom Research Division, Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Han, Jaegu (Mushroom Research Division, Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Lee, Kang-Hyo (Mushroom Research Division, Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Hong, Sungyoul (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Kim, Jong-Hoon (Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • 투고 : 2015.02.23
  • 심사 : 2015.05.19
  • 발행 : 2015.07.01

초록

Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

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참고문헌

  1. Byeon, S. E., Lee, S. Y., Kim, A. R., Lee, J., Sung, G. H., Jang, H. J., Kim, T. W., Park, H. J., Lee, S. J., Hong, S. and Cho, J. Y. (2011) Inhibition of cytokine expression by a butanol extract from Cordyceps bassiana. Pharmazie 66, 58-62.
  2. Chang, Y., Yang, S.-T., Liu, J.-H., Dong, E., Wang, Y., Cao, A., Liu, Y. and Wang, H. (2011) In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol. Lett. 200, 201-210. https://doi.org/10.1016/j.toxlet.2010.11.016
  3. Foerster, F., Braig, S., Moser, C., Kubisch, R., Busse, J., Wagner, E., Schmoeckel, E., Mayr, D., Schmitt, S., Huettel, S., Zischka, H., Mueller, R. and Vollmar, A. M. (2014) Targeting the actin cytoskeleton: selective antitumor action via trapping PKCvarepsilon. Cell Death Dis. 5, e1398. https://doi.org/10.1038/cddis.2014.363
  4. Holliday, J. C. and Cleaver, M. P. (2008) Medicinal value of the caterpillar fungi species of the genus Cordyceps (Fr.) Link (Ascomycetes). A review. Int. J. Med. Mushrooms 10, 219-234. https://doi.org/10.1615/IntJMedMushr.v10.i3.30
  5. Jayakumar, T., Chiu, C. C., Wang, S. H., Chou, D. S., Huang, Y. K. and Sheu, J. R. (2014) Anti-cancer effects of CME-1, a novel polysaccharide, purified from the mycelia of Cordyceps sinensis against B16-F10 melanoma cells. J. Cancer Res. Ther. 10, 43-49. https://doi.org/10.4103/0973-1482.131365
  6. Jin, C. Y., Kim, G. Y. and Choi, Y. H. (2008) Induction of apoptosis by aqueous extract of Cordyceps militaris through activation of caspases and inactivation of Akt in human breast cancer MDA-MB-231 Cells. J. Microbiol. Biotechnol. 18, 1997-2003.
  7. Kim, H. G., Song, H., Yoon, D. H., Song, B. W., Park, S. M., Sung, G. H., Cho, J. Y., Park, H. I., Choi, S., Song, W. O., Hwang, K. C. and Kim, T. W. (2010) Cordyceps pruinosa extracts induce apoptosis of HeLa cells by a caspase dependent pathway. J. Ethnopharmacol. 128, 342-351. https://doi.org/10.1016/j.jep.2010.01.049
  8. Kim, J. H., Lee, Y. G., Yoo, S., Oh, J., Jeong, D., Song, W. K., Yoo, B. C., Rhee, M. H., Park, J., Cha, S. H., Hong, S. and Cho, J. Y. (2013) Involvement of Src and the actin cytoskeleton in the antitumorigenic action of adenosine dialdehyde. Biochem. Pharmacol. 85, 1042-1056. https://doi.org/10.1016/j.bcp.2013.01.012
  9. Kim, J. H., Lee, Y., Sung, G. H., Kim, H. G., Jeong, D., Park, J. G., Baek, K. S., Sung, N. Y., Yang, S., Yoon, D. H., Lee, S. Y., Kang, H., Song, C., Cho, J. H., Lee, K. H., Kim, T. W. and Cho, J. Y. (2015) Antiproliferative and apoptosis-inducing activities of 4-isopropyl-2,6-bis(1-phenylethyl)phenol isolated from butanol fraction of Cordyceps bassiana. Evid. Based Complement. Alternat. Med. 2015, 739874.
  10. Kim, M. Y. and Cho, J. Y. (2013a) 20S-dihydroprotopanaxadiol, a ginsenoside derivative, boosts innate immune responses of monocytes and macrophages. J. Ginseng Res. 37, 293-299. https://doi.org/10.5142/jgr.2013.37.293
  11. Kim, M. Y. and Cho, J. Y. (2013b) 20S-dihydroprotopanaxatriol modulates functional activation of monocytes and macrophages. J. Ginseng Res. 37, 300-307. https://doi.org/10.5142/jgr.2013.37.300
  12. Kim, M. Y., Kim, J. H. and Cho, J. Y. (2014) Cytochalasin B modulates macrophage-mediated inflammatory responses. Biomol. Ther. 22, 295-300. https://doi.org/10.4062/biomolther.2014.055
  13. Kothakota, S., Azuma, T., Reinhard, C., Klippel, A., Tang, J., Chu, K., McGarry, T. J., Kirschner, M. W., Koths, K. and Kwiatkowski, D. J. (1997) Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 278, 294-298. https://doi.org/10.1126/science.278.5336.294
  14. Kundu, J., Choi, B. Y., Jeong, C.-H., Kundu, J. K. and Chun, K.-S. (2014) Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2-and Src-mediated phosphorylation of EGF receptor tyrosine kinase. Oncol. Rep. 32, 821-828.
  15. Lee, D. H., Kim, H. H., Cho, H. J., Yu, Y. B., Kang, H. C., Kim, J. L., Lee, J. J. and Park, H. J. (2014) Cordycepin-enriched WIB801C from Cordyceps militaris inhibits collagen-induced [Ca(2+)]i mobilization via cAMP-dependent phosphorylation of inositol 1, 4, 5-trisphosphate receptor in human platelets. Biomol. Ther. 22, 223-231. https://doi.org/10.4062/biomolther.2014.025
  16. Maravei, D. V., Trbovich, A. M., Perez, G. I., Tilly, K. I., Banach, D., Talanian, R. V., Wong, W. W. and Tilly, J. L. (1997) Cleavage of cytoskeletal proteins by caspases during ovarian cell death: evidence that cell-free systems do not always mimic apoptotic events in intact cells. Cell Death Differ. 4, 707-712. https://doi.org/10.1038/sj.cdd.4400311
  17. Martin, P., Pardo, J., Schill, N., Jockel, L., Berg, M., Froelich, C. J., Wallich, R. and Simon, M. M. (2010) Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics. J. Biol. Chem. 285, 18918-18927. https://doi.org/10.1074/jbc.M109.056028
  18. Mashima, T., Naito, M. and Tsuruo, T. (1999) Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis. Oncogene 18, 2423-2430. https://doi.org/10.1038/sj.onc.1202558
  19. Ng, T. B. and Wang, H. X. (2005) Pharmacological actions of Cordyceps, a prized folk medicine. J. Pharm. Pharmacol. 57, 1509-1519. https://doi.org/10.1211/jpp.57.12.0001
  20. Nunez, G., Benedict, M. A., Hu, Y. and Inohara, N. (1998) Caspases: the proteases of the apoptotic pathway. Oncogene 17, 3237-3245.
  21. Oltval, Z. N., Milliman, C. L. and Korsmeyer, S. J. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death. Cell 74, 609-619. https://doi.org/10.1016/0092-8674(93)90509-O
  22. Park, B. T., Na, K. H., Jung, E. C., Park, J. W. and Kim, H. H. (2009) Antifungal and anticancer activities of a protein from the mushroom Cordyceps militaris. Korean J. Physiol. Pharmacol. 13, 49-54. https://doi.org/10.4196/kjpp.2009.13.1.49
  23. Satzger, I., Mattern, A., Kuettler, U., Weinspach, D., Voelker, B., Kapp, A. and Gutzmer, R. (2010) MicroRNA-15b represents an independent prognostic parameter and is correlated with tumor cell proliferation and apoptosis in malignant melanoma. Int. J. Cancer 126, 2553-2562.
  24. Shinohara, K., Tomioka, M., Nakano, H., Tone, S., Ito, H. and Kawashima, S. (1996) Apoptosis induction resulting from proteasome inhibition. Biochem. J. 317, 385-388. https://doi.org/10.1042/bj3170385
  25. Twentyman, P. and Luscombe, M. (1987) A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. Br. J. Cancer 56, 279-285. https://doi.org/10.1038/bjc.1987.190
  26. Utsumi, T., Sakurai, N., Nakano, K. and Ishisaka, R. (2003) C-terminal 15 kDa fragment of cytoskeletal actin is posttranslationally N-myristoylated upon caspase-mediated cleavage and targeted to mitochondria. FEBS Lett. 539, 37-44. https://doi.org/10.1016/S0014-5793(03)00180-7
  27. Vermes, I., Haanen, C., Steffens-Nakken, H. and Reutellingsperger, C. (1995) A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J. Immunol. Methods 184, 39-51. https://doi.org/10.1016/0022-1759(95)00072-I
  28. Wu, G., Li, L., Sung, G. H., Kim, T. W., Byeon, S. E., Cho, J. Y., Park, C. W. and Park, H. J. (2011) Inhibition of 2,4-dinitrofl uorobenzene-induced atopic dermatitis by topical application of the butanol extract of Cordyceps bassiana in NC/Nga mice. J. Ethnopharmacol. 134, 504-509. https://doi.org/10.1016/j.jep.2010.12.012
  29. Yue, K., Ye, M., Zhou, Z., Sun, W. and Lin, X. (2013) The genus Cordyceps: a chemical and pharmacological review. J. Pharm. Pharmacol. 65, 474-493. https://doi.org/10.1111/j.2042-7158.2012.01601.x
  30. Zhang, G., Gurtu, V., Kain, S. R. and Yan, G. (1997) Early detection of apoptosis using a fluorescent conjugate of annexin V. Biotechniques 23, 525-531.
  31. Zhang, X., Shan, P., Alam, J., Fu, X. Y. and Lee, P. J. (2005) Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury. J. Biol. Chem. 280, 8714-8721. https://doi.org/10.1074/jbc.M408092200
  32. Zhou, X., Gong, Z., Su, Y., Lin, J. and Tang, K. (2009) Cordyceps fungi: natural products, pharmacological functions and developmental products. J. Pharm. Pharmacol. 61, 279-291. https://doi.org/10.1211/jpp.61.03.0002

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