Reactive Oxygen Species and Antioxidant Enzyme Activities in Accordance with the Cytotoxicity of Farnesol Against HL-60 Cells

Farnesol의 HL-60 세포에 대한 세포독성과 활성산소 및 항산화효소 활성 변화

  • Lim, So-Yoon (Department of Chemistry, College of Natural Science, Sangmyung University) ;
  • Park, Sie-Won (Department of Chemistry, College of Natural Science, Sangmyung University)
  • 임소윤 (상명대학교 자연과학대학 화학과) ;
  • 박시원 (상명대학교 자연과학대학 화학과)
  • Published : 2006.12.31


Farnesol in fruits, vegetables, herbs and leaves acts as bioactive component related with prevention of cancer and psychological malaise. We investigated the cytotoxic effects of farnesol on human leukemic cell, HL-60 cells, by MTT assay using 3- (4,5-Oirnethylthiazol-2-yl) -2,5-diphenyltetrazoliumbromide. Farnesol (0.1${\sim}$50 ${\mu}$g/ml) exhibited cytotoxicities against HL-60 cells in concentration and culture period dependent manner, In the cytotoxic condition induced by farnesol against HL-60 cells, the generation of reactive oxygen species such as O$_2$ and H$_2$O$_2$ were found to be considerably increased. The most prominent augmentations of O$_2$ and H$_2$O$_2$ were over five folds of controls. In an attempt to explore the response of HL-60 cells to the increased O$_2$ and H$_2$O$_2$, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities of HL-60 cells treated with farnesol were measured. SOD and GPx activities were found to be remarkably elevated by addition of farnesol showing the best results of 273% and 167% of controls, respectively: All data suggest that farnesol may have played as an apoptosis inducer in HL-60 cells via production of reactive oxygen species (ROS) and HL-60 cells may have failed to overcome the damage of ROS on account of still defcient ROS scavengers including SOD and GPx.


  1. Hyotylainena, T., Kallio, M., Kronholm, J., Kulmala, M. and Riekkolaa, M. L. : Characterization of organic compounds in aerosol particles from a coniferous forest by GC-MS. Chemoshere. 64, 1185 (2006)
  2. Guenther, A., Karl, T., Harley, P., Wiedinmyer, C., Palmer, P. L. and Geron, C. : Estimates of global terrestrial isoprene emissions using MEGAN (Model of Emissions of Gases and Aerosols from Nature). Atmospheric Chem. Phy. 6, 3181 (2006)
  3. Robert, A. R., Boris, O., Schlumpberger, R., Kaczorowskic, L. and Timothy, P. H. : Phylogenetic fragrance patterns in nicotiana sections alatae and suaveolentes. Phytochem. 67, 1931 (2006)
  4. Hakola, H., Shores, B., Arey, J. and Atkins, R. : Product formation from the gas-phase reaction of OH radical and $O_{3}$ with b-phellandrene. Environ. Sci. Technol. 27, 278 (1993)
  5. Politeo, O., Jukic, M. and Milos, M. : Chemical composition abd antioxidant capacity of free volatile aglycons from basil (Ocimum basillicum L.) compared with its essential oils. Food Chem. 101, 379 (2007)
  6. Sandip, B. B., Kamlesh, K., Bhutani, S. I., Kahn, B. L., Tekwani, Melissa, R. J., Ikhlas, A. K. and Inder, P. S. : Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues. Bioorgan. Medicin. Chem. 14, 1750 (2006)
  7. Masako, K., Yusuke, K., Hideyukia, I., Atsuko, M., Yoshiki, M., Kayoko, M. and Makoto, K. : A novel method to control the balance of skin microflora. J. Dermatol. Sci. 39, 197 (2005)
  8. Tanida, M., Niijima, A., Shen, J., Nakamura, T. and Nagai, K. : Olfactory stimulation with scent of lavender oil affects autonomic neurotransmission and blood pressure in rats. Neurosci. Lett. 398, 155 (2006)
  9. McAnally, J. A., Jung, N. and Mo, H. : Farnesyl-O-acetylhydro quinone and geranyl-O-acetylhydroquinone suppress the proliferation of murine B16 melanoma cells, human prostate and colon adenocarcinoma cells, human lung carcinoma cells, and human leukemia cells. Cancer Lett. 202, 181 (2003)
  10. Burke, Y. D., Ayoubi, A. S., Werner, S. R., McFarland, B. C., Heilman, D. K., Ruggeri, B. A. and Crowell, P. L. : Effects of the isoprenoids perillyl alcohol and farnesol on apoptosis biomarkers in pancreatic cancer chemoprevention. Anticancer Res. 22, 3127 (2002)
  11. Crowell, P. L. and Gould, M. N. : Chemoprevention of mammary cancer by monoterpenoids. Crit. Rev. Oncogen. 5, 1 (1994)
  12. Ong, T. P., Heider, R., de Conti, A., Dagli, M. L. Z. and Moreno, F. S. : Farnesol and geraniol chemopreventive activities during the initial phases of hepatocarcinogenesis involve similar on cell proliferation and DNA damage, but distinct actions actions apoptosis, plasma cholesterol and HMG-CoA reductase. Carcinogenesis 27, 1194 (2006)
  13. Culier, M. E., Bercet, C. and Richard, H. : Antioxidant constituents in sage (Salvia officinales). J. Agr. Food Chem. 42, 665 (1994)
  14. Kikuzaki, H. and Nakatani, N. : Antioxidant effects of some ginger constituents. J. Food Sci. 58, 1407 (1993)
  15. Takahashi, N., Kawada, T., Goto, Y., Yamamoto, T., Taimatsu, A., Matsui, N., Kimura, K., Saito, M., Hosokawa, M., Miyashita, K. and Fushiki, T. : Dual action of isoprenols from herbal medicines on both $PPAR{\gamma}$ and $PPAR{\alpha}$ in 3T3-L1 adipocytes and HepG2 hepatocytes. FEBS Letters 514, 315 (2002)
  16. Duncan, R. E. and Archera, M. C. : Farnesol induces thyroid hormone receptor (THR) ${\beta}1$ but inhibits THR-mediated signaling in MCF-7 human breast cancer cells. Biochem. Biophy. Res. Commun. 343, 239 (2006)
  17. Bifulco, M. : Role of the isoprenoid pathway in ras transforming activity, cytoskeleton organization, cell proliferation and apoptosis. Life Sci. 77, 1740 (2005)
  18. Bifulco, M., Laezza, C. and Aloj. S. M. : Inhibition of farnesylation blocks growth but not differentiation in FRTL-5 thyroid cells. Biochim. 81, 287 (1999)
  19. Valco, M., Keibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M. and Telser, J. L. : Free radicals and antioxidants in normal physiological functions and human disease. Intern. J. Biochem. Cell Biol. 39, 44 (2007)
  20. Bartsch, H. and Nair, J. : Chronic inflammatoion and oxidative stress in the genesis and perpetuation of cancer : Role of lipid peroxidation and DNA damage and repair. Lagenbeck's Arch. Surg. 391, 499 (2006)
  21. Kok, P. L., Shan, H. H., De Silva, R., Tan, B. K. H. and Yi, Z. Z. : Oxidative stress : Apoptosis in neuronal injury. Curr. Alzheimer. Res. 3, 327 (2006)
  22. Sisto, M., Acquafredda, A., Mitolo, V., Panaro, M. A., Lisi, S. and Saccia, M. : Polimorphonuclear cell-mediated oxidative stress : Sink for reactive oxygen species and cell various type damage. Immunopharm. Immuotox. 28, 153 (2006)
  23. Levy, A. P. : Application of pharmacogenomics in the prevention of diabetic cardiovascular disease: Mechanistic basis and clinical evidence for utilization of the haptoglobin genotype in determining benefit from antioxidant therapy. Pharmacol. Therapeu. 112, 501 (2006)
  24. Augusta, M. : NADPH oxidase-derived ROS : Key modulators of heme-induced mitochondrial stability in human neutrophils. Exper. Res. (2006) article in press
  25. Hald, A. and Lotharius, J. : Oxidative stress and inflammation in Parkinson's disease: is there a causal link- Exper. Neurol. 193, 279 (2005)
  26. Meany, D. L., Poe, B. G., Navratil, M., Moraes, C. T. and Amiaga, E. A. : Superoxide released into the mitochondrial matrix. Free Radical Biol. Med. 41, 950 (2006)
  27. Bulteau, A. L., Szweda, L. I. and Friguet, B. : Mitochondrial protein oxidation and degradation in response to oxidative stress and aging. Exper. Gerontol. 41, 653 (2006)
  28. Lee, D. W. and Opanashuk, L. A. : Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury. Neurotoxicol. 25, 925 (2004)
  29. Mizutania, H., Tada-Oikawa, S., Hirakua, Y., Kojima, M. and Kwanishi, S. : Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sci. 76, 1439 (2005)
  30. Schmackerm, P. T. : Reactive oxygen species in cancer cells: Live by sword, die by sword. Cancer Cell 10, 175 (2006)
  31. Tokarska-Schlattner, M., Michael Zaug., Zuppinger, C., Wallimann, T. and Schlattner, U. : Review article. New insights into doxorubicin-induced cardiotoxicity: The critical role of cellular energetics. J. Mol. Cell. Cardiol. 41, 389, (2006)
  32. Yen, H. C., Chang, H. M., Majimam H. J., Chen, F. Y. and Li, S. H. : Levels of reactive oxygen species and primary antioxidant enzymes in WI38 versus transformed WI38 cells following bleomcyin treatment. Free Radical Biol. Med. 38, 950 (2005)
  33. Mosmann, T. : Rapid colorimetric assay for cellular growth and survival : Application to proliferation and cytotoxicity assays. J. Immunol. Meth. 65, 55 (1983)
  34. Markert, M., Andrews, P. C. and Babior, B. M. : Measurement of $O_{2}$ - production by human neutrophils. The preparation and assay of NADPH oxidase-containing particles from neutrophils. Meth. Enzymol. 105, 358 (1984)
  35. Paglia, D. E. and Valentine, W. N. : Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Labor. Chem. Med. 70, 158 (1967)
  36. McCord, J. M. and Fridovich, I. : Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244, 6049 (1969)
  37. Flohe, L. and Otting, F. : Superoxide dismutase assays. Meth. Enzymol. 105, 93 (1984)
  38. Gunzler, W. A., Kremers, H. and Flohe, L. : An improved coupled test procedure for glutathione peroxidase in blood. Z. Klin. Chem. Klin. Biochem. 12, 444 (1974)
  39. Clairborne, A. : Catalase activity. In: R. A. Greenwald, Editor, Handbook of Methods for Oxygen Radical Research, CRC press, Boca Raton, USA, p. 383 (1985)
  40. Reiter, R. J. : Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB Journal 9, 528 (1995)
  41. Olguin-Martinez, M., Mendieta-Condado, E., Martha Contreras-Zentella, M., Escamilla, J. E., Aranda-Fraustro, A., El-Hafidi, M. and Hernandez-Munoz. R. : Rate of oxidant stress regulates balance between rat gastric mucosa proliferation and apoptosis. Free Rad. Biol. Med. 41, 1325 (2006)
  42. Sandra, M., Cardoso, A., Rego, C., Penacho, N. and Oliveira, C. R. : Apoptotic cell death induced by hydrogen peroxide in NT2 parental and mitochondrial DNA depleted cells. Neurochem. Internat. 45, 693 (2004)
  43. Schrader, M. and Dariush, H. : Fahimi A protective association between catalase and isocitrate lyase in peroxisomes. Arch. Biochem. Biophy. 435, 243 (2005)
  44. Zhou, Z. and Kang, Y. J. : Cellular and subcellular localization of catalase in the heart of transgenic mice. J. of Histochem. Cytochem. 48, 585 (2000)