Food Science and Biotechnology

, Volume 19, Issue 5, pp 1325–1332 | Cite as

α-pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells

  • Kyong-Suk Jin
  • Min-Ji Bak
  • Mira Jun
  • Ho-Jin Lim
  • Wan-Keun Jo
  • Woo-Sik JeongEmail author
Research Article


The volatile organic compounds (VOCs) -dlimonene, α-pinene, and isoprene-are widely used in scented products including food flavorings, air fresheners, and cosmetics. The effects of these VOCs on cell viability, oxidative stress generation, and the related molecular events were investigated in A549 and HepG2 cells. α-Pinene induced cell death, reactive oxygen species (ROS) generation, and reporter gene activities of antioxidant response element (ARE), activator protein 1 (AP-1), and nuclear factor (NF)-κB. α-Pinene stimulated the redoxsensitive transcription factors such as nuclear factor E2-related factor 2 (Nrf2) and NF-κB. Their down stream targets including heme oxygenase 1, inducible nitric oxide synthase, and cyclooxygenase 2 also increased after treatment with α-pinene. Moreover, α-pinene-induced oxidative stress-related signaling pathways could be connected by mitogen-activated protein kinases. Conversely, α-pinene-mediated cell death, ROS formation, and AP-1 induction were inhibited by an antioxidant, N-acetyl-l-cysteine. Thus, α-pinene can induce the cell death possibly by modulating oxidative stress-related signaling pathways which can be reversed by an antioxidant treatment.


volatile organic compound α-pinene oxidative stress cytotoxicity activator protein 1 


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  1. 1.
    Loza-Tavera H. Monoterpenes in essential oils. Biosynthesis and properties. Adv. Exp. Med. Biol. 464: 49–62 (1999)Google Scholar
  2. 2.
    Sharkey TD. Isoprene synthesis by plants and animals. Endeavour 20: 74–78 (1996)CrossRefGoogle Scholar
  3. 3.
    Hernandez-Munoz P, Catala R, Gavara R. Food aroma partition between packaging materials and fatty food simulants. Food Addit. Contam. 18: 673–682 (2001)CrossRefGoogle Scholar
  4. 4.
    Kwon KD, Jo WK, Lim HJ, Jeong WS. Characterization of emissions composition for selected household products available in Korea. J. Hazard. Mater. 148: 192–198 (2007)CrossRefGoogle Scholar
  5. 5.
    Wagner KH, Elmadfa I. Biological relevance of terpenoids. Overview focusing on mono-, di-, and tetraterpenes. Ann. Nutr. Metab. 47: 95–106 (2003)CrossRefGoogle Scholar
  6. 6.
    Betteridge DJ. What is oxidative stress? Metabolis. 49: 3–8 (2000)CrossRefGoogle Scholar
  7. 7.
    Kang KW, Lee SJ, Kim SG. Molecular mechanism of Nrf2 activation by oxidative stress. Antioxid. Redox Sign. 7: 1664–1673 (2005)CrossRefGoogle Scholar
  8. 8.
    Karin M, Takahashi T, Kapahi P, Delhase M, Chen Y, Makris C, Rothwarf D, Baud V, Natoli G, Guido F, Li N. Oxidative stress and gene expression: The AP-1 and NF-kappaB connections. Biofactors 15: 87–89 (2001)CrossRefGoogle Scholar
  9. 9.
    Karin M, Liu Z, Zandi E. AP-1 function and regulation. Curr. Opin. Cell Biol. 9: 240–246 (1997)CrossRefGoogle Scholar
  10. 10.
    Mercurio F, Manning AM. NF-kappaB as a primary regulator of the stress response. Oncogene 18: 6163–6171 (1999)CrossRefGoogle Scholar
  11. 11.
    Li N, Hao M, Phalen RF, Hinds WC, Nel AE. Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects. Clin. Immunol. 109: 250–265 (2003)CrossRefGoogle Scholar
  12. 12.
    Chen Q, Olashaw N, Wu J. Participation of reactive oxygen species in the lysophosphatidic acid-stimulated mitogen-activated protein kinase kinase activation pathway. J. Biol. Chem. 270: 28499–28502 (1995)CrossRefGoogle Scholar
  13. 13.
    Yu R, Lei W, Mandlekar S, Weber MJ, Der CJ, Wu J, Kong AN. Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals. J. Biol. Chem. 274: 27545–27552 (1999)CrossRefGoogle Scholar
  14. 14.
    Jiao HL, Zhao BL. Cytotoxic effect of peroxisome proliferator fenofibrate on human HepG2 hepatoma cell line and relevant mechanisms. Toxicol. Appl. Pharm. 185: 172–179 (2002)CrossRefGoogle Scholar
  15. 15.
    Sekiya M, Hiraishi A, Touyama M, Sakamoto K. Oxidative stress induced lipid accumulation via SREBP1c activation in HepG2 cells. Biochem. Bioph. Res. Co. 375: 602–607 (2008)CrossRefGoogle Scholar
  16. 16.
    Jeong WS, Keum YS, Chen C, Jain MR, Shen G, Kim JH, Li W, Kong AN. Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J. Biochem. Mol. Biol. 38: 167–176 (2005)Google Scholar
  17. 17.
    Jeong WS, Kim IW, Hu R, Kong AN. Modulatory properties of various natural chemopreventive agents on the activation of NFkappaB signaling pathway. Pharm. Res. 21: 661–670 (2004)CrossRefGoogle Scholar
  18. 18.
    Jeong WS, Kim IW, Hu R, Kong AN. Modulation of AP-1 by natural chemopreventive compounds in human colon HT-29 cancer cell line. Pharm. Res. 21: 649–660 (2004)CrossRefGoogle Scholar
  19. 19.
    Halliwell B, Gutteridge JM. Free Radicals in Biology and Medicine. 4th ed. Oxford University Press, New York, NY, USA. p. 851 (2007)Google Scholar
  20. 20.
    Jeong WS, Jun M, Kong AN. Nrf2: A potential molecular target for cancer chemoprevention by natural compounds. Antioxid. Redox Sign. 8: 99–106 (2006)CrossRefGoogle Scholar
  21. 21.
    Surh YJ, Kundu JK, Na HK, Lee JS. Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J. Nutr. 135: 2993S–3001S (2005)Google Scholar
  22. 22.
    Cao J, Liu Y, Jia L, Jiang LP, Geng CY, Yao XF, Kong Y, Jiang BN, Zhong LF. Curcumin attenuates acrylamide-induced cytotoxicity and genotoxicity in HepG2 cells by ROS scavenging. J. Agr. Food Chem. 56: 12059–12063 (2008)CrossRefGoogle Scholar
  23. 23.
    Toyooka T, Ibuki Y. Cigarette sidestream smoke induces phosphorylated histone H2AX. Mutat. Res. 676: 34–40 (2009)Google Scholar
  24. 24.
    Sies H, Cadenas E. Oxidative stress: Damage to intact cells and organs. Philos. T. Roy. Soc. B. 311: 617–631 (1985)CrossRefGoogle Scholar
  25. 25.
    Rice-Evans C, Burdon R. Free radical-lipid interactions and their pathological consequences. Prog. Lipid Res. 32: 71–110 (1993)CrossRefGoogle Scholar
  26. 26.
    Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. 44: 239–267 (2004)CrossRefGoogle Scholar
  27. 27.
    Nishida N, Tamotsu S, Nagata N, Saito C, Sakai A. Allelopathic effects of volatile monoterpenoids produced by Salvia leucophylla: Inhibition of cell proliferation and DNA synthesis in the root apical meristem of Brassica campestris seedlings. J. Chem. Ecol. 31: 1187–1203 (2005)CrossRefGoogle Scholar
  28. 28.
    Singh HP, Batish DR, Kaur S, Arora K, Kohli RK. α-Pinene inhibits growth and induces oxidative stress in roots. Ann. Bot.- London 98: 1261–1269 (2006)CrossRefGoogle Scholar
  29. 29.
    Falk AA, Hagberg MT, Lof AE, Wigaeus-Hjelm EM, Wang ZP. Uptake, distribution, and elimination of α-pinene in man after exposure by inhalation. Scand. J. Work Env. Hea. 16: 372–378 (1990)Google Scholar
  30. 30.
    Nielsen GD, Larsen ST, Hougaard KS, Hammer M, Wolkoff P, Clausen PA, Wilkins CK, Alarie Y. Mechanisms of acute inhalation effects of (+) and (-)-α-pinene in BALB/c mice. Basic Clin. Pharmacol. 96: 420–428 (2005)CrossRefGoogle Scholar
  31. 31.
    Farombi EO, Surh YJ. Heme oxygenase-1 as a potential therapeutic target for hepatoprotection. J. Biochem. Mol. Biol. 39: 479–491 (2006)Google Scholar
  32. 32.
    Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 12: 9–18 (2002)CrossRefGoogle Scholar
  33. 33.
    Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH. Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr. Rev. 22: 153–183 (2001)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Netherlands 2010

Authors and Affiliations

  • Kyong-Suk Jin
    • 1
  • Min-Ji Bak
    • 1
  • Mira Jun
    • 2
  • Ho-Jin Lim
    • 3
  • Wan-Keun Jo
    • 3
  • Woo-Sik Jeong
    • 1
    Email author
  1. 1.School of Food and Life Sciences, College of Biomedical Science and Engineering, Center of Smart Foods & DrugsInje UniversityGimhae, GyeongnamKorea
  2. 2.Division of Food ScienceDong-A UniversityBusanKorea
  3. 3.Department of Environmental EngineeringKyungpook National UniversityDaeguKorea

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