DOI QR코드

DOI QR Code

Terpinen-4-ol Induces Autophagic and Apoptotic Cell Death in Human Leukemic HL-60 Cells

  • Published : 2013.12.31

Abstract

Background: Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Materials and Methods: The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.

References

  1. Banjerdpongchai R, Kongtawelert P, Khantamat O, et al (2010). Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells. J Hematol Oncol, 3, 50-65. https://doi.org/10.1186/1756-8722-3-50
  2. Banjerdpongchai R, Punyat, P, Nakrob A, et al (2011). 4'-Hydroxycinnamaldehyde from Alpinia galanga (Linn.) induces human leukemic cell apoptosis via mitochondrial and endoplasmic reticulum stress pathways. Asian Pac J Cancer Prev, 12, 593-8.
  3. Banjerdpongchai R, Suwannachot K, Rattanapanone V, Sripanidkulchai B (2008). Ethanolic rhizome extract from Kaempferia parviflora Wall. ex. Baker induces apoptosis in HL-60 cells. Asian Pac J Cancer Prev, 9, 595-600.
  4. Baumgartner HK, Gerasimenko JV, Thorne C, et al (2007). Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins. Am J Physiol Gastrointest Liver Physiol, 293, 296-307. https://doi.org/10.1152/ajpgi.00103.2007
  5. Bursch W (2001). The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ, 8, 569-81. https://doi.org/10.1038/sj.cdd.4400852
  6. Calcabrini A, Stringaro A, Toccacieli L, et al (2004). Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells. J Invest Dermatol, 122, 349-60. https://doi.org/10.1046/j.0022-202X.2004.22236.x
  7. Chen N, Debnath J (2010). Autophagy and tumorigenesis. FEBS Lett, 584, 1427-35. https://doi.org/10.1016/j.febslet.2009.12.034
  8. Fiorini C, Menegazzi M, Padroni C, et al (2013). Autophagy induced by p53-reactivating molecules protects pancreatic cancer cells from apoptosis. Apoptosis, 18, 337-4. https://doi.org/10.1007/s10495-012-0790-6
  9. Girard-Lalancette K, Pichette A, Legault J (2009). Sensitive cellbased assay using DCFH oxidation for the determination of pro- and antioxidant properties of compounds and mixtures: Analysis of fruit and vegetable juices. Food Chem, 115, 720-6. https://doi.org/10.1016/j.foodchem.2008.12.002
  10. Greay SJ, Ireland DJ, Kissick HT, et al (2010). Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol. Cancer Chemother Pharmacol, 65, 877-88. https://doi.org/10.1007/s00280-009-1093-7
  11. Guo Y, Srinivasula SM, Druilhe A, et al (2002). Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J Biol Chem, 277, 13430-7. https://doi.org/10.1074/jbc.M108029200
  12. Hart PH, Brand C, Carson CF, et al (2000). Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res, 49, 619-26. https://doi.org/10.1007/s000110050639
  13. He C, Klionsky DJ (2009). Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet, 43, 67-93. https://doi.org/10.1146/annurev-genet-102808-114910
  14. Jeenapongsa R, Yoovathaworn K, Sriwatanakul KM, et al (2003). Anti-inflammatory activity of (E)-1-(3,4-dimethoxyphenyl) butadiene from Zingiber cassumunar Roxb. J Ethnopharmacol, 87, 143-8. https://doi.org/10.1016/S0378-8741(03)00098-9
  15. Kang R, Tang DL, Lotze MT, Zeh HJ (2011). Apoptosis to autophagy switch triggered by the MHC class III-encoded receptor for advanced glycation endproducts (RAGE). Autophagy, 7, 91-3. https://doi.org/10.4161/auto.7.1.13852
  16. Karmakar S, Banik NL, Patel SJ, Ray SK (2007). Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells. Apoptosis, 12, 671-84. https://doi.org/10.1007/s10495-006-0024-x
  17. Khaw-on P, Banjerdpongchai R (2012). Induction of intrinsic and extrinsic apoptosis pathways in the human leukemic MOLT-4 cell line by terpinen-4-ol. Asian Pac J Cancer Prev, 13, 3073-6. https://doi.org/10.7314/APJCP.2012.13.7.3073
  18. Kim EH, Sohn S, Kwon HJ, et al (2007). Sodium selenite induces superoxide-mediated mitochondrial damage and subsequent autophagic cell death in malignant glioma cells. Cancer Res, 67, 6314-24. https://doi.org/10.1158/0008-5472.CAN-06-4217
  19. Lahlou S, Interaminense LF, Leal-Cardoso JH, Duarte GP (2003). Antihypertensive effects of the essential oil of Alpinia zerumbet and its main constituent, terpinen-4-ol, in DOCAsalt hypertensive conscious rats. Fundam Clin Pharmacol, 17, 323-30. https://doi.org/10.1046/j.1472-8206.2003.00150.x
  20. Laurent A, Nicco C, Chereau C, et al (2005). Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res, 65, 948-56.
  21. Lewis JS, Meeke K, Osipo C, et al (2005). Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation. J Natl Cancer Inst, 97, 1746-59. https://doi.org/10.1093/jnci/dji400
  22. Loughlin R, Gilmore BF, McCarron PA, Tunney MM (2008). Comparison of the cidal activity of tea tree oil and terpinen-4-ol against clinical bacterial skin isolates and human fibroblast cells. Lett Appl Microbiol, 46, 428-33. https://doi.org/10.1111/j.1472-765X.2008.02334.x
  23. Mondello F, De Bernardis F, Girolamo A, et al (2006). In vivo activity of terpinen-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azolesusceptible and -resistant human pathogenic Candida species. BMC Infect Dis, 6, 158. https://doi.org/10.1186/1471-2334-6-158
  24. Naves T, Jawhari S, Jauberteau MO, et al (2013). Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl(2). Biochem Pharmacol, 85, 1153-61. https://doi.org/10.1016/j.bcp.2013.01.022
  25. Nishida K, Yamaguchi O, Otsu K (2008). Crosstalk between autophagy and apoptosis in heart disease. Circ Res, 103, 343-51. https://doi.org/10.1161/CIRCRESAHA.108.175448
  26. Paisooksantivatana S, Bua-in Y (2009). Essential oil and antioxidant activity of Cassumunar Ginger (Zingiberaceae: Zingiber montanum (Koenig) Link ex Dietr.) collected from various parts of Thailand. Kasetsart J (Natural Science), 43, 467-75.
  27. Pazyar N, Yaghoobi R, Bagheran, N, Kazerouni A (2013). A review of applications of tea tree oil in dermatology. Int J Dermatol, 52, 784-90. https://doi.org/10.1111/j.1365-4632.2012.05654.x
  28. Rikiishi H (2012). Novel Insights into the Interplay between Apoptosis and Autophagy. Int J Cell Biol, 2012, 317645.
  29. Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ (2007). Potential therapeutic applications of autophagy. Nat Rev Drug Discov, 6, 304-12. https://doi.org/10.1038/nrd2272
  30. Saeki K, Yuo A, Okuma E, et al (2000). Bcl-2 down-regulation causes autophagy in a caspase-independent manner in human leukemic HL60 cells. Cell Death Differ, 7, 1263-9. https://doi.org/10.1038/sj.cdd.4400759
  31. Santin G, Bottone MG, Malatesta M, et al (2013). Regulated forms of cell death are induced by the photodynamic action of the fluorogenic substrate, hypocrellin B-acetate. J Photochem Photobiol B, 125, 90-7. https://doi.org/10.1016/j.jphotobiol.2013.05.006
  32. Singh NP (2000). A simple method for accurate estimation of apoptotic cells. Exp Cell Res, 256, 328-37. https://doi.org/10.1006/excr.2000.4810
  33. Wei Y, Pattingre S, Sinha S, et al (2008). JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell, 30, 678-88. https://doi.org/10.1016/j.molcel.2008.06.001
  34. Wu CS, Chen YJ, Chen JJ, et al (2012). Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo. Evid Based Complement Alternat Med, 2012, 818261.
  35. Yousefi S, Perozzo R, Schmid I, et al (2006). Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol, 8, 1124-32. https://doi.org/10.1038/ncb1482
  36. Zorov DB, Juhaszova M, Yaniv Y, et al (2009). Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovasc Res, 83, 213-25. https://doi.org/10.1093/cvr/cvp151

Cited by

  1. Ebb-and-Flow of Macroautophagy and Chaperone-Mediated Autophagy in Raji Cells Induced by Starvation and Arsenic Trioxide vol.15, pp.14, 2014, https://doi.org/10.7314/APJCP.2014.15.14.5715
  2. Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6939
  3. Anti-tumor Effects and Apoptosis Induction by Realgar Bioleaching Solution in Sarcoma-180 Cells in Vitro and Transplanted Tumors in Mice in Vivo vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2883
  4. Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3987
  5. Evaluation of Antioxidant and Anticancer Activity of Steam Extract from The Bamboo Species vol.42, pp.5, 2014, https://doi.org/10.5658/WOOD.2014.42.5.543
  6. Stigmalactam from Orophea Enterocarpa Induces Human Cancer Cell Apoptosis Via a Mitochondrial Pathway vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10397
  7. Autophagy-associated Targeting Pathways of Natural Products during Cancer Treatment vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10557
  8. Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways vol.37, pp.1, 2016, https://doi.org/10.1007/s13277-015-3774-7
  9. Terpinen-4-ol inhibits colorectal cancer growth via reactive oxygen species vol.14, pp.2, 2017, https://doi.org/10.3892/ol.2017.6370
  10. Apoptosis Induction via ATM Phosphorylation, Cell Cycle Arrest, and ER Stress by Goniothalamin and Chemodrugs Combined Effects on Breast Cancer-Derived MDA-MB-231 Cells vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/7049053
  11. (Nees) Radlk fresh leaf ethanolic extract on human breast cancer MDA-MB-231 regulated cell death vol.40, pp.9, 2018, https://doi.org/10.1177/1010428318800182
  12. Potential anti-mutagenicity, antioxidant, and anti-inflammatory capacities of the extract from perilla seed meal pp.01458884, 2018, https://doi.org/10.1111/jfbc.12556